Implementation of a Multidisciplinary Inpatient Cardiology Service to Improve Heart Failure Outcomes in Guyana.

BACKGROUND: Guyana is a small developing country with a high burden of cardiovascular disease and extensive barriers to optimal care delivery. We investigated the effectiveness of a newly established multidisciplinary inpatient cardiology service in this setting. METHODS: We performed an interrupted time-series cohort study of heart failure (HF) patients admitted to the Georgetown Public Hospital Corporation from January to December 2015 and July 2016 to December 2017. The primary outcome was discharge on guideline-directed medical therapy (GDMT). Secondary outcomes included length of hospitalization and all-cause mortality. RESULTS: We identified 740 patients, 347 (46.9%) of whom were admitted after service implementation. The postimplementation cohort was more likely to be discharged on a beta-blocker (66.6% vs 41.7%; P < .01) and mineralocorticoid receptor antagonist (31.7% vs 15.3%; P = .01). They were also more likely to undergo echocardiography (60.8% vs 40.5%; P < .01) and chest x-rays (70.6% vs 46.6%; P < .01). Hospitalization length (10.0 ± 13.1 vs 9.8 ± 10.1 days) and readmissions within 90 days (19.0% vs 19.1%) were not significantly different. There were fewer deaths in the postimplementation cohort compared with the preimplementation cohort (12/347 vs 28/393). CONCLUSIONS: Establishment of a multidisciplinary inpatient cardiology service demonstrated increased adherence to GDMT without extending length of hospitalization.

ß-blocker Therapy is Not Associated with Reductions in Angina or Cardiovascular Events After Coronary Artery Bypass Graft Surgery: Insights from the IMAGINE Trial.

PURPOSE: To evaluate whether ß-blockers were associated with a reduction in cardiovascular events or angina after Coronary Artery Bypass Graft (CABG) surgery, in otherwise stable low-risk patients during a mid-term follow-up. METHODS: We performed a post-hoc analysis of the IMAGINE (Ischemia Management with Accupril post-bypass Graft via Inhibition of angiotensin coNverting Enzyme) trial, which tested the effect of Quinapril in 2553 hemodynamically stable patients with left ventricular ejection fraction (LVEF) >40 %, after scheduled CABG. The association between ß-blocker therapy and the incidence of cardiovascular events (death, cardiac arrest, myocardial infarction, revascularizations, angina requiring hospitalization, stroke or hospitalization for heart failure) or angina that was documented to be due to underlying ischemia was tested with Cox regression and propensity adjusted analyses. RESULTS: In total, 1709 patients (76.5 %) were using a ß-blocker. Patients had excellent control of risk factors; with mean systolic blood pressure being 121 ± 14 mmHg, mean LDL cholesterol of 2.8 mmol/l, 59% of patients received statins and 92% of patients received antiplatelet therapy. During a median follow-up of 33 months, ß-blocker therapy was not associated with a reduction in cardiovascular events (hazard ratio 0.97; 95 % confidence interval 0.74-1.27), documented angina (hazard ratio 0.85; 95 % confidence interval 0.61-1.19) or any of the individual components of the combined endpoint. There were no relevant interactions for demographics, comorbidities or surgical characteristics. Propensity matched and time-dependent analyses revealed similar results. CONCLUSIONS: ß-blocker therapy after CABG is not associated with reductions in angina or cardiovascular events in low-risk patients with preserved LVEF, and may not be systematically indicated in such patients.

The Guyana Program to Advance Cardiac Care: A Model for Equitable Cardiovascular Care Delivery.

Guyana is one of the poorest countries in South America, with the highest rate of cardiovascular mortality on the continent. As is the case in many low- and middle-income countries, cardiovascular care is available through the private sector but is not accessible to much of the urban and rural poor. We present the 10-year experience of the Guyana Program to Advance Cardiac Care (GPACC), an academic partnership aiming to provide high-quality, equitable cardiovascular care in Georgetown's only public hospital. We discuss the implementation of a cardiac care program using the World Health Organization Framework for Action, outlining vital components for care delivery in resource-limited settings. GPACC was able to demonstrate that targeted investment, education of clinicians, and cohesive healthcare delivery strategies can contribute to sustainable service delivery for Guyana's largest burden of disease. This structured approach may provide lessons for implementation of similar programs in other resource-limited settings. Highlights: In many LMICs, specialized cardiovascular care is available in the private, but not public, sector.The WHO Framework for Action can guide development of sustainable programs in low-resource settings.GPACC can serve as a successful and innovative model for delivery of sustainable cardiovascular care.

Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease.

BACKGROUND: Data supporting the prognostic significance of high-sensitivity C-reactive protein (hs-CRP) are derived largely from individuals with no overt coronary artery disease or from patients with acute coronary syndromes. In contrast, the ability of hs-CRP to predict outcomes in patients with stable coronary artery disease and the prognostic significance of the Centers for Disease Control/American Heart Association hs-CRP cut points in such a population remain relatively unexplored. METHODS AND RESULTS: We measured hs-CRP in 3771 patients with stable coronary artery disease from the Prevention of Events With Angiotensin-Converting Enzyme Inhibition (PEACE) trial, a randomized placebo-controlled trial of the angiotensin-converting enzyme inhibitor trandolapril. Patients were followed up for a median of 4.8 years for cardiovascular death, myocardial infarction, or stroke, as well as new heart failure and diabetes. After adjustment for baseline characteristics and treatments, higher hs-CRP levels, even >1 mg/L, were associated with a significantly greater risk of cardiovascular death, myocardial infarction, or stroke (hs-CRP 1 to 3 mg/L: adjusted hazard ratio, 1.39; 95% CI, 1.06 to 1.81; P=0.016; hs-CRP >3 mg/L: adjusted hazard ratio, 1.52; 95% CI, 1.15 to 2.02; P=0.003). Similarly, elevated hs-CRP levels were an independent predictor of new heart failure (adjusted P<0.001 for trend) and new diabetes (adjusted P<0.001 for trend). There were no significant interactions between hs-CRP levels and the effects of trandolapril on any of the above outcomes. CONCLUSIONS: In stable coronary artery disease, an elevated hs-CRP level, even >1 mg/L, is a significant predictor of adverse cardiovascular events independently of baseline characteristics and treatments. An elevated hs-CRP does not appear to identify patients with stable coronary artery disease and preserved ejection fraction who derive particular benefit from angiotensin-converting enzyme inhibition.

High mortality without ESCAPE: the registry of heart failure patients receiving pulmonary artery catheters without randomization.

BACKGROUND: In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), there was no difference in days alive and out of the hospital for patients with decompensated heart failure randomly assigned to therapy guided by pulmonary artery catheter (PAC) plus clinical assessment versus clinical assessment alone. The external validity of these findings is debated. METHODS AND RESULTS: ESCAPE sites enrolled 439 patients receiving PAC without randomization in a prospective registry. Baseline characteristics, pertinent trial exclusion criteria, reasons for PAC use, hemodynamics, and complications were collected. Survival was determined from the National Death Index and the Alberta Registry. On average, registry patients had lower blood pressure, worse renal function, less neurohormonal antagonist therapy, and higher use of intravenous inotropes compared with trial patients. Although clinical assessment anticipated less volume overload and greater hypoperfusion among the registry population, measured filling pressures were similarly elevated in the registry and trial patients, whereas measured perfusion was slightly higher among registry patients. Registry patients had longer hospitalization (13 vs 6 days, P < .001) and higher 6-month mortality (34% vs 20%, P < .001) than trial patients. CONCLUSIONS: The decision to use PAC without randomization identified a population with higher disease severity and risk of mortality. This prospective registry highlights the complex context of patient selection for randomized trials.

Use and impact of inotropes and vasodilator therapy in hospitalized patients with severe heart failure.

BACKGROUND: Treatment of decompensated heart failure often includes the use of intravenous vasoactive medications, but the effect on outcome has not been clearly defined. METHODS: Data from 433 patients enrolled in the ESCAPE trial were analyzed to determine 6-month risks of all-cause mortality and all-cause mortality plus rehospitalization associated with the use of vasodilators, inotropes, and their combination. Patients had a mean left ventricular ejection fraction of 19%, 6-minute walk distance of 414 ft, and systolic blood pressure of 106 mm Hg. The main outcome measure was multivariable risk-adjusted 6-month hazard ratios (HRs). RESULTS: Overall 6-month mortality was 19%. Risk-adjusted HRs were not statistically significant for vasodilators (1.39, 95% CI 0.64-3.00), but were significant for inotropes (2.14, 95% CI 1.10-4.15) and the combination (4.81, 95% CI 2.34-9.90). Risk-adjusted 6-month mortality plus rehospitalization HRs were not significant for vasodilators (1.20, 95% CI 0.81-1.78, P = .37), but were significant for inotropes (1.96, 95% CI 1.37-2.82, P < .001) and their combination (2.90, 95% CI 1.88-4.48, P = .001). The decision to use vasodilators or inotropes was determined by hemodynamic parameters and renal function, but the main factor was treatment site. CONCLUSIONS: In ESCAPE, the choice of medications was mainly determined by the treatment site. Use of inotropic agents was associated with adverse outcomes, whereas the use of vasodilators was not. Inotropes in combination with vasodilators identified a group with the highest mortality. Prospective studies are needed to establish the appropriate use of vasoactive medications in this population.

Changes in ventricular size and function in patients treated with valsartan, captopril, or both after myocardial infarction.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have been shown to attenuate left ventricular (LV) enlargement in association with reducing mortality after myocardial infarction (MI). Preclinical data suggest that angiotensin receptor blockers (ARBs) may have similar structural and functional effects after MI. The Valsartan in Acute Myocardial Infarction (VALIANT) Echo study was designed to test the hypothesis that the ARB valsartan, either alone or in combination with captopril, could attenuate progressive LV enlargement or improve LV ejection fraction to a greater extent than captopril alone. METHODS AND RESULTS: Six hundred ten patients enrolled in the main VALIANT study who experienced MI and evidence of LV dysfunction, heart failure, or both were enrolled in the VALIANT Echo study. Patients were randomized to receive valsartan 160 mg PO BID, captopril 50 mg PO TID, or valsartan 80 mg PO BID plus captopril 50 mg PO TID between 1 and 10 days after MI. Six hundred three patients had echocardiograms of sufficient quality for quantitative analysis. Echocardiograms were digitized, and endocardial borders were traced manually from 2 short-axis and 2 apical views. Ventricular volumes, ejection fractions, combined areas, and infarct segment length were measured, and changes in echocardiographic measures from baseline to 20 months were compared between treatment groups. Baseline clinical and echocardiographic characteristics were similar in the 3 treatment arms. The changes from baseline to 20 months in all echocardiographic parameters were similar in all 3 treatment arms. Baseline echocardiographic measures of ejection fraction, end-diastolic volume, and infarct segment length were highly predictive of outcomes including total mortality, death or hospitalization for heart failure, or death or any cardiovascular event (heart failure, MI, stroke, resuscitated sudden death), even after adjustment for known covariates. CONCLUSIONS: Treatment with the ACE inhibitor captopril, valsartan, or the combination of captopril plus valsartan resulted in similar changes in cardiac volume, ejection fraction, and infarct segment length between baseline and 20 months after MI. Baseline echocardiographic measures were powerfully and independently predictive of all major outcomes.

Angiotensin-converting enzyme inhibition in patients with coronary artery disease and preserved left ventricular function Ischemia Management with Accupril post-bypass graft via inhibition of angiotensin-converting enzyme (IMAGINE) compared with the other major trials in coronary artery disease.

It has been hypothesized that angiotensin-converting enzyme (ACE) inhibition, independent from its effect on ventricular function and blood pressure, could affect the atherosclerotic process and reduce the incidence of ischemic events and its complications. Several large clinical outcome trials were designed to test this hypothesis: QUIET, HOPE, EUROPA, PEACE, and IMAGINE. The results of the PEACE study were recently reported, leaving the IMAGINE study as the last chapter in our efforts to evaluate the role of ACE inhibition in coronary artery disease with preserved left ventricular function. In this report, we compare these studies with respect to their methodology and patient population and analyze the unique nature of the last ongoing study, IMAGINE. The reported studies show that patients with coronary artery disease who are at low-to-moderate or high risk should receive an ACE inhibitor if tolerated. However, when the absolute risk of a patient decreases, and intensive contemporary management is given, with good control of risk factors, the absolute and perhaps relative benefits of an ACE inhibitor decrease and their routine use in these patients may not be warranted. The role of ACE inhibition started early post-coronary artery bypass graft in patients with preserved left ventricular function, and intensive contemporary management remains to be determined and should get answered by the IMAGINE study. Moreover, the IMAGINE population is not only a lower risk population than those enrolled in HOPE or EUROPA, but also the risk for this population is bimodal in nature (early post-revascularization inflammation and thrombosis vs long-term atherosclerosis progression) and may provide further insight into underlying mechanisms.

Predictors of late development of heart failure in stable survivors of myocardial infarction: the CARE study.

OBJECTIVES: We sought to determine the predictors of heart failure (HF) development in long-term survivors of myocardial infarction (MI). BACKGROUND: Modern strategies of acute MI care have resulted in an increasing proportion of survivors at heightened risk of future non-fatal events, including HF. METHODS: We assessed the risk of developing HF in 3860 stable MI patients without a previous history of HF, who were enrolled in the Cholesterol And Recurrent Events (CARE) trial a median of 10 months post MI. Baseline characteristics of patients who did or did not develop HF during the five years of observation were assessed. RESULTS: A total of 243 patients (6.3%) developed HF in a linear pattern at a rate of 1.3%/year. Heart failure development markedly increased the risk of death (hazard ratio 10.2, 95% confidence interval 7.7 to 13.5). Fifty-seven patients (23.5%) who developed HF had a recurrent MI between enrollment and the onset of HF, increasing the risk fivefold. The most important predictors of HF were age and left ventricular ejection fraction. Other predictors included diabetes, history of hypertension, previous MI, and baseline heart rate. Moderate exercise three or more times per week was independently associated with a 30% lower risk of HF. CONCLUSIONS: Heart failure post MI occurs in a time-dependent fashion, which is usually not a direct consequence of a detectable interim MI. Patients who experience late-onset HF have a 10-fold increased risk of death compared with other MI survivors. Baseline characteristics can risk stratify patients at high risk of subsequent HF.

Ischemia Management with Accupril post bypass Graft via Inhibition of angiotensin coNverting enzyme (IMAGINE): a multicentre randomized trial - design and rationale.

BACKGROUND: Coronary artery bypass grafting (CABG) remains the revascularization treatment of choice for patients with severely symptomatic or life-threatening coronary artery disease (CAD). However, 9% to 25% of the patients undergoing CABG will suffer a recurrent ischemic event such as death, recurrent infarction, angina or repeat revascularization. The pathophysiological processes particular to the CABG procedure that may affect graft endothelial function are most active in the early phase after surgery. Angiotensin-converting enzyme (ACE) inhibition has been shown to be effective in reducing or preventing ischemic events in patients with and without left ventricular dysfunction, and in those at high risk for CAD. Nonetheless, no large clinical trail has investigated this role of ACE inhibition in preventing ischemic events early after CABG. OBJECTIVE: The Ischemia Management with Accupril post bypass Graft via Inhibition of angiotensin coNverting Enzyme (IMAGINE) study addressed whether ACE inhibition initiated early after CABG improves short and long term outcomes in patients after CABG. PATIENTS AND METHODS: This multicentre, multinational trial recruited 2204 patients with an uncomplicated course early after CABG from 55 to 65 medical care facilities in Canada, The Netherlands, Belgium and France. Eligible patients with normal left ventricular function were randomly assigned to placebo or quinapril (titrated up to 40 mg daily where possible) within seven to 10 days after CABG. All patients were followed up closely for a minimum of 12 months after random placement. The median treatment period is expected to be approximately 27 months.

Changing preferences for survival after hospitalization with advanced heart failure.

OBJECTIVES: This study was designed to analyze how patient preferences for survival versus quality-of-life change after hospitalization with advanced heart failure (HF). BACKGROUND: Although patient-centered care is a priority, little is known about preferences to trade length of life for quality among hospitalized patients with advanced HF, and it is not known how those preferences change after hospitalization. METHODS: The time trade-off utility, symptom scores, and 6-min walk distance were measured in 287 patients in the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheter Effectiveness) trial at hospitalization and again during 6 months after therapy to relieve congestion. RESULTS: Willingness to trade was bimodal. At baseline, the median trade for better quality was 3 months' survival time, with a modest relation to symptom severity. Preference for survival time was stable for most patients, but increase after discharge occurred in 98 of 145 (68%) patients initially willing to trade survival time, and was more common with symptom improvement and after therapy guided by pulmonary artery catheters (p = 0.034). Adjusting days alive after hospital discharge for patients' survival preference reduced overall days by 24%, with the largest reduction among patients dying early after discharge (p = 0.0015). CONCLUSIONS: Preferences remain in favor of survival for many patients despite advanced HF symptoms, but increase further after hospitalization. The bimodal distribution and the stability of patient preference limit utility as a trial end point, but support its relevance in design of care for an individual patient.

Mitral regurgitation in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both: prognostic significance and relation to ventricular size and function.

AIMS: Mitral regurgitation (MR) confers independent risk in patients with acute myocardial infarction. We utilized data from the VALsartan In Acute myocardial iNfarcTion echo study to relate baseline MR to left ventricular (LV) size, shape, and function, and to assess the relationship between baseline MR and progression of MR and cardiovascular (CV) outcomes. METHODS AND RESULTS: We studied 496 patients with heart failure (HF) and/or systolic dysfunction after MI who underwent echocardiography at a median of 5 days after MI. MR severity, quantified as the regurgitant jet area/left atrial area ratio, was assessed at baseline, one and 20 months post-MI and related to LV size, shape, function, and clinical outcomes. Increased MR at baseline was associated with larger LV end-diastolic and end-systolic volumes, increased sphericity index, and reduced ejection fraction (P trend < 0.001). Moderate-severe MR was an independent predictor of total mortality [adjusted hazard ratio (HR) 2.4 (1.1-5.3)], CV mortality [adjusted HR 2.7 (1.2-6.1)], hospitalization for HF [adjusted HR 2.5 (1.1-5.5)], or death or HF hospitalization [adjusted HR 2.5 (1.4-4.6)]. Patients with progression of MR during the first post-MI month were substantially more likely to die or develop HF (adjusted HR per increased MR grade 3.0, 95% CI 1.8-4.9). Progression of MR over 20 months in survivors was associated with increased hospitalizations for HF (P < 0.001). CONCLUSION: Following high-risk myocardial infarction, baseline mitral regurgitant severity is associated with larger LV volumes and worse LV function. Both baseline MR severity and progression of MR are associated with an increased likelihood of adverse outcomes.