Dobutamine as bridge to angiotensin-converting enzyme inhibitor-nitrate therapy in endstage heart failure.

BACKGROUND: Intravenous inotropic intervention in congestive heart failure is generally associated with a poor prognosis and is largely used as a "bridge" to mechanical support or heart transplantation. HYPOTHESIS: We hypothesized that the inotropic support afforded by dobutamine may serve as a bridge to the introduction and intensification of angiotensin-converting enzyme (ACE) inhibitor-nitrate therapy. METHODS: We studied the efficacy of transitioning inotrope-dependent patients in endstage heart failure from intravenous dobutamine to high-dose ACE inhibitor-nitrates, with 1-year follow-up. Forty-nine sequential dobutamine-dependent patients with left ventricular ejection fraction (LVEF) 17+/-17% were treated with increasing lisinopril (1.9+/-1.5 to 46+/-28 mg/day) and isosorbide dinitrate (7+/-6 to 229+/-161 mg/day). Outpatient dobutamine was continued or repeat infusions pursued, as indicated, and dobutamine was tapered when feasible. RESULTS: During the following year, 14 of 49 patients required repeat dobutamine, with home treatment with dobutamine for 6.3+/-3.7 months (n = 5). At 1 year, New York Heart Association (NYHA) classification improved from 3.6+/-0.5 to 1.9+/-1.0, p < 0.0001; yearly hospitalizations fell from 2.7+/-2.3 to 1.2+/-3.0, p = 0.02; and LVEF rose from 17+/-7% to 24+/-11%, p < 0.0001. At 1 year, 14 patients who remained dobutamine dependent had significantly more severe symptoms than dobutamine-independent patients (n = 35). Transplant or death occurred in 7 of 14 patients with follow-up dobutamine, and in 5 of 35 patients free of subsequent dobutamine, p = 0.03. Patients with poor outcome (transplant n = 10, death n = 12) continued to be more limited (NYHA 2.7+/-0.9 vs. 1.7+/-0.9, p = 0.0002), with more follow-up hospitalizations (3.6+/-5.4 vs. 0.6+/-0.8, p = 0.0004), and no improvement in LVEF (17+/-8vs. 28+/-11%, p = 0.003). CONCLUSIONS: Of the patients on dobutamine inotropic support, 70% were successfully transitioned to ACE inhibitor-nitrate therapy, with improved symptoms and LVEF, and with reduced hospitalizations and follow-up dobutamine or transplant. Thirty percent of patients with continued need for dobutamine had a significantly poorer 1-year clinical outcome.

A time-to-treatment analysis in the medicine versus angiography in thrombolytic exclusion (MATE) trial.

Patients with acute coronary syndromes who are considered ineligible for thrombolytic therapy are at high risk of recurrent ischemia and death. This trial randomized 201 patients to triage angiography in the first 24 hours of hospital admission versus conventional medical care. Of the 165 patients who underwent angiography that was either protocol-driven or on the basis of physician preference, those who underwent angiography within 6 hours of symptom onset had a reduction in early and late adverse events. The rates of in-hospital recurrent ischemia were 15.4%, 15.4%, 17.5%, 32.4%, and 38.5%, respectively (P = 0.01 for trend), and rates of cumulative recurrent myocardial infarction or death were 0%, 12.8%, 10.0%, 11.8%, and 7.7%, respectively (P = 0.48 for trend) for patients who underwent angiography at 0-6, 6-12, 12-24, 24-48, and over 48 hours, respectively from symptom onset. Future trials of invasive versus conservative therapy should focus on performing angiography within 6 hours of symptom onset.

Impaired culprit vessel flow in acute coronary syndromes ineligible for thrombolysis.

The majority of patients with acute myocardial infarction and other acute coronary syndromes (ACS) are considered ineligible for thrombolysis and do not routinely receive reperfusion therapy. We hypothesized that predictors and outcomes of angiographically impaired culprit vessel flow can be identified and compared. This trial evaluated the outcomes following triage angiography in acute coronary syndromes ineligible for thrombolytic therapy. Eligible patients (n=201) with<24 hours of symptoms were randomized to early triage angiography and subsequent therapies based on the angiogram versus conventional medical therapy. This analysis was performed in 165 patients, from experimental and control arms, in whom angiography was performed on the index hospitalization with the outcome of interest being target vessel flow (Thrombolysis In Myocardial Infarction [TIMI] grades 0 to 2) on initial angiography. Patients with and without impaired culprit lesion flow were similar with respect to age, gender, diabetes, and prior coronary disease. A family history of premature coronary disease was more common in those with impaired flow, 50.0 versus 28.5% (p=0.02). Abnormal culprit vessel flow was found in 19.2% of patients who underwent angiography within 6 hours of symptom onset; however, after 24 hours this rate was reduced to 11.7%. Impaired culprit lesion flow can be expected in approximately 20% of patients presenting with ACS who are ineligible for reperfusion therapy by conventional guidelines and therefore represents an opportunity for early intervention within 6 hours of the onset of symptoms in these patients.

Reversal of heart failure remodeling in women.

Epidemiological studies suggest that women with heart failure differ from men with heart failure in that their survival is better. Therapeutic trials have not clearly demonstrated a survival benefit for women. This study was to determine the tolerance for high doses of angiotensin-converting enzyme (ACE) inhibitor-nitrates in women versus men and to compare their symptomatic response, exercise tolerance, and ventricular functional improvement over 1 year. Eighty-eight sequential patients with heart failure, 54 men and 34 women with left ventricular ejection fraction < or = 35%, were prospectively followed for 1 year. For all patients, ACE inhibitor-nitrate therapy was intensified. Each patient had three 6-monthly echocardiograms at baseline, at 6 months, and at 1 year, and metabolic stress testing. Patients were 57.3 +/- 12.3 years old, with New York Heart Association (NYHA) class severity 2.6 +/- 1.0. Lisinopril dosages were raised from 14 +/- 14 mg/day to 57 +/- 26 mg/day, isosorbide mononitrate from 15 +/- 27 mg/day to 126 +/- 72 mg/day, and carvedilol (n = 34) to 17 +/- 16 mg/day. Women and men were epidemiologically comparable, with similar baseline echocardiographic parameters (left ventricular ejection fraction 19% +/- 7% versus 17% +/- 6%, respectively). Both tolerated up-titration in medical therapy. Final 12-month ejection fractions were equivalent for women and men at 34% +/- 17% and 34% +/- 13%, respectively, with similar improvements in left ventricular diameters. At 1 year, women had higher resting heart rates and remained more symptomatic with lower exercise capacity. However, the relative changes in NYHA status and aerobic capacity were similar for women and men. Thus, both women and men tolerated uptitrated ACE inhibitor-nitrate medical therapy, with comparable reversal of heart failure remodeling. Although women continued to be more symptomatic than men, relative improvements in symptomatic status, in exercise capacity, and in hospitalization rate were equivalent.

Impact of left ventricular size on pharmacologic reverse remodeling in heart failure.

BACKGROUND AND HYPOTHESIS: Although medical therapy may normalize echocardiographic left ventricular (LV) systolic function in selected patients with cardiomyopathy, other patients experience no change or a further deterioration in heart failure remodeling. Our aim was to determine what clinical or echocardiographic parameters predict a beneficial therapeutic response. METHODS: We prospectively followed biannual clinical and echocardiographic assessments in 215 patients. Forty-six of these patients ("Nonresponders") experienced no change or a decline in LV ejection fraction at 6 months. Of the 148 patients who improved LV function, 21 ("Responders") normalized LV systolic function at 6 months. Only Responders (n = 21) and Nonresponders (n = 46) were compared. RESULTS: On average, these 67 patients were 54 +/- 12 years old with 4.5 +/- 3.3 years of heart failure. At 6 months, following up-titration of angiotensin-converting enzyme inhibitors and nitrates, Responder LV ejection fraction rose from 22 +/- 6 to 50 +/- 5% with improvement in New York Heart Association classification (2.6 +/- 0.8 to 1.5 +/- 0.8, p = 0.001). These patients had significantly more favorable clinical and echocardiographic outcomes versus Nonresponders despite comparable medical therapy. All baseline demographic, clinical, and echocardiographic variables were equivalent, except for initial LV end-diastolic diameter which differentiated Nonresponders (7.1 +/- 0.7 cm) from Responders (6.1 +/- 0.8 cm), p = 0.007. CONCLUSION: Thus, although heart failure therapy improves LV systolic function in a majority of patients, with normalization in up to 10% of patients, significant LV enlargement may render remodeling unresponsive to pharmacologic intervention, with a potential future need for alternative mechanical or surgical intervention.

Efficacy of low-dose amiodarone in the prevention of paroxysmal atrial fibrillation resistant to type IA antiarrhythmic drugs.

The efficacy and safety of low-dose amiodarone (Cordarone; Wyeth-Ayerst, Philadelphia, PA) was assessed in 62 symptomatic patients with paroxysmal atrial fibrillation who were resistant to at least two types of IA drugs. The beneficial response to this treatment was defined as a reduction in paroxysmal atrial fibrillation of greater than or equal to 50% within 1 month. Of the 42 patients (67.7%) who were responders, 39 (62.9%) were completely free of episodes. Intolerable side effects were seen in 12 patients (19.3%). Tolerable side effects were encountered by 73% of patients. Most of the adverse effects were transient and responded to a reduction in the dose. In conclusion, (1) low-dose amiodarone produces a beneficial response in the prevention of paroxysmal atrial fibrillation, and (2) low-dose amiodarone is well tolerated.

A prospective randomized trial of triage angiography in acute coronary syndromes ineligible for thrombolytic therapy. Results of the medicine versus angiography in thrombolytic exclusion (MATE) trial.

OBJECTIVES: The purpose of this study was to determine if early triage angiography with revascularization, if indicated, favorably affects clinical outcomes in patients with suspected acute myocardial infarction who are ineligible for thrombolysis. BACKGROUND: The majority of patients with acute myocardial infarction and other acute coronary syndromes are considered ineligible for thrombolysis and therefore are not afforded the opportunity for early reperfusion. METHODS: This multicenter, prospective, randomized trial evaluated in a controlled fashion the outcomes following triage angiography in acute coronary syndromes ineligible for thrombolytic therapy. Eligible patients (n=201) with <24 h of symptoms were randomized to early triage angiography and subsequent therapies based on the angiogram versus conventional medical therapy consisting of aspirin, intravenous heparin, nitroglycerin, beta-blockers, and analgesics. RESULTS: In the triage angiography group, 109 patients underwent early angiography and 64 (58%) received revascularization, whereas in the conservative group, 54 (60%) subsequently underwent nonprotocol angiography in response to recurrent ischemia and 33 (37%) received revascularization (p=0.004). The mean time to revascularization was 27+/-32 versus 88+/-98 h (p=0.0001) and the primary endpoint of recurrent ischemic events or death occurred in 14 (13%) versus 31 (34%) of the triage angiography and conservative groups, respectively (45% risk reduction, 95% CI 27-59%, p=0.0002). There were no differences between the groups with respect to initial hospital costs or length of stay. Long-term follow-up at a median of 21 months revealed no significant differences in the endpoints of late revascularization, recurrent myocardial infarction, or all-cause mortality. CONCLUSIONS: Early triage angiography in patients with acute coronary syndromes who are not eligible for thrombolytics reduced the composite of recurrent ischemic events or death and shortened the time to definitive revascularization during the index hospitalization. Despite more frequent early revascularization after triage angiography, we found no long-term benefit in cardiac outcomes compared with conservative medical therapy with revascularization prompted by recurrent ischemia.

The use of intraaortic balloon counterpulsation as an adjunct to reperfusion therapy in cardiogenic shock.

Modern coronary care unit interventions have not reduced the high mortality rate associated with cardiogenic shock due to acute myocardial infarction. Results with thrombolytic therapy have also been disappointing because of poor infarct artery patency rates in a low coronary flow state. Percutaneous transluminal coronary angioplasty appears to be a beneficial intervention, but the technique is not available at most hospitals. Intraaortic balloon counterpulsation provides temporary hemodynamic and clinical improvement in the majority of patients with cardiogenic shock. The use of intraaortic counterpulsation to augment patency rates with thrombolytic therapy or to stabilize patients for transfer to a hospital with angioplasty services appears to be a promising strategy for hospitals without an interventional cardiac catheterization laboratory.

Early ambulation following 6 French diagnostic left heart catheterization: a prospective randomized trial.

Outpatient cardiac catheterization is frequently performed, but the optimal recovery time after sheath removal has not been defined. Left heart catheterization was performed via the femoral artery utilizing 6 French catheters on 323 outpatients. One hundred thirty-five patients were randomized to ambulate at a mean of 2.5 hr (group 1) after puncture site compression, whereas 188 patients were randomized to ambulate at a mean of 4.1 hr (group 2). Telephone follow-up occurred within 48 hr. A small hematoma (< 5 cm) occurred in 2 (1.6%) patients in group 1 and in 4 (2.4%) patients in group 2. These results indicate that it is safe to ambulate patients 2.5 hr following 6 French diagnostic heart catheterization.

Use of intraaortic balloon counterpulsation in patients presenting with cardiogenic shock: observations from the GUSTO-I Study. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.

OBJECTIVES: We sought to examine the use, complications and outcomes with early intraaortic balloon counterpulsation (IABP) in patients presenting with cardiogenic shock complicating acute myocardial infarction and treated with thrombolytic therapy. BACKGROUND: The use of IABP in patients with cardiogenic shock is widely accepted; however, there is a paucity of information on the use of this technique in patients with cardiogenic shock who are treated with thrombolytic therapy. METHODS: Patients who presented within 6 h of chest pain onset were randomized to one of four thrombolytic regimens. Cardiogenic shock was not an exclusion criterion, and data for these patients were prospectively collected. Patients presenting with shock were classified into early IABP (insertion within one calendar day of enrollment) or no IABP (insertion on or after day 2 or never). RESULTS: There were 68 (22%) IABP placements in 310 patients presenting with shock. Early IABP use occurred in 62 patients (20%) and none in 248 (80%). Most IABP use occurred in the United States (59 of 68 IABP placements) involving 32% of U.S. patients presenting with shock. Despite more adverse events in the early IABP group and more episodes of moderate bleeding, this cohort showed a trend toward lower 30-day and 1-year mortality rates. CONCLUSIONS: IABP appears to be underutilized in patients presenting with cardiogenic shock, both within and outside the United States. Early IABP institution is associated with an increased risk of bleeding and adverse events but a trend toward lower 30-day and 1-year all-cause mortality.

Thrombolysis plus aortic counterpulsation: improved survival in patients who present to community hospitals with cardiogenic shock.

OBJECTIVES: We sought to explore the potential benefit of combining intraaortic balloon counterpulsation (IABP) with thrombolysis for acute myocardial infarction (MI) complicated by cardiogenic shock. BACKGROUND: In community hospitals, this condition is usually managed with thrombolysis alone. METHODS: We reviewed the charts of 335 patients from two community hospitals who presented with acute MI and had cardiogenic shock between 1985 and 1995. RESULTS: Of 46 patients who underwent thrombolysis within 12 h of acute infarction with confirmed cardiogenic shock, 27 underwent IABP and 19 did not. Age, systolic blood pressure with shock, pulmonary artery catheter use, pulmonary capillary wedge pressure and the incidence of diabetes mellitus and anterior MI did not differ between groups. Patients treated with IABP were somewhat more likely to have prior MI and had a significantly greater cardiac index (2.0 vs. 1.5 liters/min per m2, p = 0.04). Although no deaths occurred within 2 h of presentation, patients not treated with IABP tended to die earlier (6.8 +/- 5 vs. 23.8 +/- 19 h, p = 0.13). Patients treated with IABP had a significantly higher rate of community hospital survival (93% vs. 37%, p = 0.0002), and more of them were transferred for revascularization (85% vs. 37%). Of 30 patients transferred for revascularization, 27 underwent angioplasty or bypass surgery; hospital survival was 74%. Patients treated with IABP also had a significantly higher overall hospital and 1-year survival rate (67% vs. 32%, p = 0.019). CONCLUSIONS: Survival may be enhanced and transfer for revascularization facilitated when community hospitals use both thrombolysis and IABP to treat patients with acute MI complicated by cardiogenic shock.

Practice guidelines for the treatment of heart failure: a commentary on the facts you need to know. Agency for Health Care Policy and Research.

The federal Agency for Health Care Policy and Research has published its second set of guidelines in the field of internal medicine. These guidelines outline a comprehensive plan for the treatment of heart failure. They focus on the practical aspects of the management of patients with heart failure due to reduced left ventricular systolic performance (ejection fractions < 35% to 40%). They also offer expert opinion in the diagnosis and evaluation of heart failure and review clinical criteria for admission and discharge of these patients. Prevention of heart failure is a major focus of these current guidelines.

Unstable angina: clinical practice guidelines for diagnosis and management. Agency for Health Care Policy and Research.

Unstable angina is one of the most common reasons for hospital admission in the United States and causes substantial morbidity and mortality. Diagnosis of unstable angina is complicated by the dynamic range of presentations, which can vary between atypical chest pain and acute myocardial infarction. Overcautious management can result in unnecessary hospital admission, whereas inappropriate conservative strategies can cause cardiac injury and death. To define treatment strategies for these patients, the US Agency for Health Care Policy and Research in March 1994 published guidelines on the diagnosis and management of unstable angina. The emphasis is on diagnosis or exclusion of coronary artery disease, establishment of the patient's risk for adverse outcome, and triage to the most appropriate treatment regimen. The guidelines emphasize the use of aspirin, heparin sodium, nitroglycerin, and beta-blockers as the core therapy. Appropriate strategies are reviewed, starting with intensive medical management and ending with patient care after discharge. Many physicians will probably modify their approach to the diagnosis and treatment of unstable angina on the basis of these new guidelines.

Treatment strategies for acute myocardial infarction complicated by cardiogenic shock in a community hospital.

The risk and benefits of three treatment strategies were examined in 64 consecutive patients with acute myocardial infarction and cardiogenic shock. Thirteen patients received thrombolytic therapy (group 1), 29 patients received intra-aortic balloon pump counterpulsation support (group 2), and 22 patients were treated with combined thrombolytic therapy and intra-aortic balloon pump counterpulsation support (group 3). The groups were similar in regard to age, sex, medical history, hemodynamic data, and extent of coronary artery disease. Survival was improved in patients treated with combined thrombolytic therapy and intra-aortic balloon pump counterpulsation support (group 1, 23 percent; group 2, 28 percent; and group 3, 68 percent; p = 0.0049). Seven percent of the patients who remained at the community hospital survived vs 69 percent who were transferred to a tertiary care center (p < 0.001), and 17 percent survived who were treated medically vs 71 percent who received revascularization (p < 0.001). These findings suggest that patients who present to a community hospital in cardiogenic shock can have their conditions stabilized, and they can then be transferred to a tertiary care hospital for revascularization and have the same outcome as patients who initially present to tertiary care hospitals.

Complications of intraaortic balloon counterpulsation insertion in patients receiving thrombolytic therapy for acute myocardial infarction.

This study retrospectively examines 38 patients who presented with acute myocardial infarction requiring intraaortic balloon pump counterpulsation. Two groups of patients were identified. Group I consisted of patients with acute myocardial infarction treated with intraaortic balloon pump without thrombolytic therapy. Group II consisted of patients treated with intraaortic balloon pump after receiving intravenous thrombolytic therapy. These groups were compared and contrasted with regard to previously identified complications associated with intraaortic balloon pump counterpulsation including loss of limb and mortality. The need for surgery, embolectomy, and drainage of hematoma were also evaluated. The need for surgery in group II (11%) and in both groups combined (7%) is lower than is generally reported in literature (range 11.6% to 34%). In addition, no patients experienced a loss of limb and no patients in the study had severe life-threatening iatrogenic morbidity or mortality. While mortality was not an end point in this study, it was noted that there was an increased survival rate in group II patients with 61% surviving until the time of hospital discharge. Also, eight out of 14 patients in group II who underwent intraaortic balloon pump counterpulsation for cardiogenic shock survived until the time of discharge. This represents a 57% survival rate for patients presenting with cardiogenic shock. We conclude that intraaortic balloon pumps can be inserted safely following thrombolytic therapy in a community hospital.