Suresh R. Mulukutla

Association Between Extracellular Matrix Expansion Quantified by Cardiovascular Magnetic Resonance and Short-Term Mortality

Background— Extracellular matrix expansion may be a fundamental feature of adverse myocardial remodeling, it appears to be treatable, and its measurement may improve risk stratification. Yet, the relationship between mortality and extracellular matrix is not clear because of difficulties with its measurement. To assess its relationship with outcomes, we used novel, validated cardiovascular magnetic resonance techniques to quantify the full spectrum of extracellular matrix expansion not readily detectable by conventional cardiovascular magnetic resonance. Methods and Results— We recruited 793 consecutive patients at the time of cardiovascular magnetic resonance without amyloidosis or hypertrophic cardiomyopathy as well as 9 healthy volunteers (ages 20–50 years). We measured the extracellular volume fraction (ECV) to quantify the extracellular matrix expansion in myocardium without myocardial infarction. ECV uses gadolinium contrast as an extracellular space marker based on T1 measures of blood and myocardium pre— and post–gadolinium contrast and hematocrit measurement. In volunteers, ECV ranged from 21.7% to 26.2%, but in patients it ranged from 21.0% to 45.8%, indicating considerable burden. There were 39 deaths over a median follow-up of 0.8 years (interquartile range 0.5–1.2 years), and 43 individuals who experienced the composite end point of death/cardiac transplant/left ventricular assist device implantation. In Cox regression models, ECV related to all-cause mortality and the composite end point (hazard ratio, 1.55; 95% confidence interval, 1.27–1.88 and hazard ratio, 1.48; 95% confidence interval, 1.23–1.78, respectively, for every 3% increase in ECV), adjusting for age, left ventricular ejection fraction, and myocardial infarction size. Conclusions— ECV measures of extracellular matrix expansion may predict mortality as well as other composite end points (death/cardiac transplant/left ventricular assist device implantation).

A comparison of bare-metal and drug-eluting stents for off-label indications.

BACKGROUND Recent reports suggest that off-label use of drug-eluting stents is associated with an increased incidence of adverse events. Whether the use of bare-metal stents would yield different results is unknown. METHODS We analyzed data from 6551 patients in the National Heart, Lung, and Blood Institute Dynamic Registry according to whether they were treated with drug-eluting stents or bare-metal stents and whether use was standard or off-label. Patients were followed for 1 year for the occurrence of cardiovascular events and death. Off-label use was defined as use in restenotic lesions, lesions in a bypass graft, left main coronary artery disease, or ostial, bifurcated, or totally occluded lesions, as well as use in patients with a reference-vessel diameter of less than 2.5 mm or greater than 3.75 mm or a lesion length of more than 30 mm. RESULTS Off-label use occurred in 54.7% of all patients with bare-metal stents and 48.7% of patients with drug-eluting stents. As compared with patients with bare-metal stents, patients with drug-eluting stents had a higher prevalence of diabetes, hypertension, renal disease, previous percutaneous coronary intervention and coronary-artery bypass grafting, and multivessel coronary artery disease. One year after intervention, however, there were no significant differences in the adjusted risk of death or myocardial infarction in patients with drug-eluting stents as compared with those with bare-metal stents, whereas the risk of repeat revascularization was significantly lower among patients with drug-eluting stents. CONCLUSIONS Among patients with off-label indications, the use of drug-eluting stents was not associated with an increased risk of death or myocardial infarction but was associated with a lower rate of repeat revascularization at 1 year, as compared with bare-metal stents. These findings support the use of drug-eluting stents for off-label indications.

A Prospective, Randomized Clinical Trial of Hemodynamic Support With Impella 2.5 Versus Intra-Aortic Balloon Pump in Patients Undergoing High-Risk Percutaneous Coronary Intervention The PROTECT II Study

Background— Although coronary artery bypass grafting is generally preferred in symptomatic patients with severe, complex multivessel, or left main disease, some patients present with clinical features that make coronary artery bypass grafting clinically unattractive. Percutaneous coronary intervention with hemodynamic support may be feasible for these patients. Currently, there is no systematic comparative evaluation of hemodynamic support devices for this indication. Methods and Results— We randomly assigned 452 symptomatic patients with complex 3-vessel disease or unprotected left main coronary artery disease and severely depressed left ventricular function to intra-aortic balloon pump (IABP) (n=226) or Impella 2.5 (n=226) support during nonemergent high-risk percutaneous coronary intervention. The primary end point was the 30-day incidence of major adverse events. A 90-day follow-up was required, as well, by protocol. Impella 2.5 provided superior hemodynamic support in comparison with IABP, with maximal decrease in cardiac power output from baseline of −0.04±0.24 W in comparison with −0.14±0.27 W for IABP (P=0.001). The primary end point (30-day major adverse events) was not statistically different between groups: 35.1% for Impella 2.5 versus 40.1% for IABP, P=0.227 in the intent-to-treat population and 34.3% versus 42.2%, P=0.092 in the per protocol population. At 90 days, a strong trend toward decreased major adverse events was observed in Impella 2.5–supported patients in comparison with IABP: 40.6% versus 49.3%, P=0.066 in the intent-to-treat population and 40.0% versus 51.0%, P=0.023 in the per protocol population, respectively. Conclusions— The 30-day incidence of major adverse events was not different for patients with IABP or Impella 2.5 hemodynamic support. However, trends for improved outcomes were observed for Impella 2.5–supported patients at 90 days. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00562016.

Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission

AIMS Diabetes may promote myocardial extracellular matrix (ECM) expansion that increases vulnerability. We hypothesized that: (i) type 2 diabetes would be associated with quantitative cardiovascular magnetic resonance (CMR) measures of myocardial ECM expansion, i.e. extracellular volume fraction (ECV); (ii) medications blocking the renin-angiotensin-aldosterone system (RAAS) would be associated with lower ECV; and (iii) ECV in diabetic individuals would be associated with mortality and/or incident hospitalization for heart failure. METHODS AND RESULTS We enrolled 1176 consecutive patients referred for CMR without amyloidosis and computed ECV from measures of the haematocrit and myocardial and blood T1 pre- and post-contrast. Linear regression modelled ECV; Cox regression modelled mortality and/or hospitalization for heart failure. Diabetic individuals (n = 231) had higher median ECV than those without diabetes (n = 945): 30.2% (IQR: 26.9-32.7) vs. 28.1% (IQR: 25.9-31.0), respectively, P < 0.001). Diabetes remained associated with higher ECV in models adjusting for demographics, comorbidities, and medications (P < 0.001). Renin-angiotensin-aldosterone system blockade was associated with lower ECV (P = 0.028) in multivariable linear models. Over a median of 1.3 years (IQR: 0.8-1.9), 38 diabetic individuals had events (21 incident hospitalizations for heart failure; 24 deaths), and ECV was associated with these events (HR: 1.52, 95% CI: 1.21-1.89 per 3% ECV increase) in multivariable Cox regression models. CONCLUSION Diabetes is associated with increased ECV. Extracellular volume fraction detects amelioration of ECM expansion associated with RAAS blockade, and is associated with mortality and/or incident hospitalization for heart failure in diabetic individuals. Extracellular matrix expansion may be an important intermediate phenotype in diabetic individuals that is detectable and treatable.

Low Prevalence of “Ideal Cardiovascular Health” in a Community-Based Population The Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) Study

Background— Cardiovascular health is a new construct defined by the American Heart Association (AHA) as part of its 2020 Impact Goal definition. The applicability of this construct to community-based populations and the distributions of its components by race and sex have not been reported. Methods and Results— The AHA construct of cardiovascular health and the AHA ideal health behaviors index and ideal health factors index were evaluated among 1933 participants (mean age 59 years; 44% blacks; 66% women) in the community-based Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. One of 1933 participants (0.1%) met all 7 components of the AHAs definition of ideal cardiovascular health. Less than 10% of participants met ≥5 components of ideal cardiovascular health in all subgroups (by race, sex, age, and income level). Thirty-nine subjects (2.0%) had all 4 components of the ideal health behaviors index and 27 (1.4%) had all 3 components of the ideal health factors index. Blacks had significantly fewer ideal cardiovascular health components than whites (2.0±1.2 versus 2.6±1.4; P <0.001). After adjustment by sex, age, and income level, blacks had 82% lower odds of having ≥5 components of ideal cardiovascular health (odds ratio 0.18, 95% confidence interval, 0.10 to 0.34; P <0.001). No interaction was found between race and sex. Conclusion— The prevalence of ideal cardiovascular health is extremely low in a middle-aged community-based study population. Comprehensive individual and population-based interventions must be developed to support the attainment of the AHA′s 2020 Impact Goal for cardiovascular health. # Clinical Perspective {#article-title-31}Background— Cardiovascular health is a new construct defined by the American Heart Association (AHA) as part of its 2020 Impact Goal definition. The applicability of this construct to community-based populations and the distributions of its components by race and sex have not been reported. Methods and Results— The AHA construct of cardiovascular health and the AHA ideal health behaviors index and ideal health factors index were evaluated among 1933 participants (mean age 59 years; 44% blacks; 66% women) in the community-based Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. One of 1933 participants (0.1%) met all 7 components of the AHAs definition of ideal cardiovascular health. Less than 10% of participants met ≥5 components of ideal cardiovascular health in all subgroups (by race, sex, age, and income level). Thirty-nine subjects (2.0%) had all 4 components of the ideal health behaviors index and 27 (1.4%) had all 3 components of the ideal health factors index. Blacks had significantly fewer ideal cardiovascular health components than whites (2.0±1.2 versus 2.6±1.4; P<0.001). After adjustment by sex, age, and income level, blacks had 82% lower odds of having ≥5 components of ideal cardiovascular health (odds ratio 0.18, 95% confidence interval, 0.10 to 0.34; P<0.001). No interaction was found between race and sex. Conclusion— The prevalence of ideal cardiovascular health is extremely low in a middle-aged community-based study population. Comprehensive individual and population-based interventions must be developed to support the attainment of the AHA′s 2020 Impact Goal for cardiovascular health.

Real-world use of the Impella 2.5 circulatory support system in complex high-risk percutaneous coronary intervention: The USpella Registry

Objectives: We report on the real‐world, multicenter experience of the Impella 2.5 circulatory support system during high‐risk PCI, a subset of the larger USpella Registry. Background: Standard of care for most patients with compromised ventricular function with multivessel or high‐risk coronary lesions has been coronary artery bypass grafting. In poor operative candidates, high‐risk PCI is increasingly considered, despite an increased risk for periprocedural hemodynamic compromise. Methods: 175 consecutive patients who underwent high‐risk PCI with prophylactic support of the Impella 2.5 were evaluated. The primary safety endpoint was the incidence of major adverse cardiac events (MACE) at 30 days. Secondary endpoints included safety and efficacy related to the device and patient outcomes, including survival at 12 months. Results: Overall angiographic revascularization was successful in 99% of patients and in 90% of those with multivessel revascularization, resulting in a reduction of the mean SYNTAX score post‐PCI from 36 ± 15 to 18 ± 15 (P < 0.0001) and an improvement of the ejection fraction (from 31 ± 15% to 36 ± 14%, P < 0.0001). In 51% of patients, the functional status improved by one or more NYHA class (P < 0.001). At 30‐day follow‐up, the rate of MACE was 8%, and survival was 96%, 91%, and 88% at 30 days, 6 months, and 12 months, respectively. Conclusions: The use of Impella 2.5 in high‐risk PCI appeared feasible and safe in the real‐world setting. The utilization of the Impella 2.5 was successful, resulting in favorable short‐ and midterm angiographic, procedural and clinical outcomes.

Extracorporeal Membrane Oxygenation for Advanced Refractory Shock in Acute and Chronic Cardiomyopathy

BACKGROUND Extracorporeal membrane oxygenation (ECMO) has been used to obtain rapid resuscitation and stabilization in advanced refractory cardiogenic shock (CS), but clear strategies to optimize outcomes and minimize futile support have not been established. METHODS We retrospectively reviewed our experience with ECMO in patients with advanced refractory CS, after an acute myocardial infarct (AMI) compared with patients receiving ECMO after an acute decompensating chronic cardiomyopathy (CCM). RESULTS Between January 2003 and February 2009, 33 patients required ECMO support for advanced refractory CS secondary to AMI (AMI-CS) and 9 patients were supported by ECMO in the presence of an acutely decompensated CCM (CCM-CS). Survival at 30 days, 1 and 2 years for patients with AMI-CS, was 64%, 48%, and 48% compared with 56%, 11%, and 11% at the same time points for those with CCM-CS (p = 0.05). In the AMI-CS group, 14 of 33 (42%) patients were weaned directly from ECMO after revascularization; 15 of 33 (45%) patients were bridged to ventricular assist device (VAD) support and subsequently either underwent heart transplantation (n = 6), were successfully weaned from VAD (n = 2) or died while on VAD support (n = 7). In the CCM-CS group, 7 patients were bridged to VAD support (77%), with 1 patient surviving after VAD weaning. CONCLUSIONS Extracorporeal membrane oxygenation in advanced refractory AMI-CS is associated with acceptable outcomes in a well-selected population. The ECMO in patients with an acute decompensation of a chronic CM should be carefully considered, to avoid futile support.

Increased Adverse Events After Percutaneous Coronary Intervention in Patients With COPD: Insights From the National Heart, Lung, and Blood Institute Dynamic Registry

BACKGROUND Previous studies have demonstrated that patients with COPD are at higher risk for death after percutaneous coronary intervention (PCI), but other clinical outcomes and possible associations with adverse events have not been described. METHODS Using waves 1 through 5 (1999-2006) of the National Heart, Lung, and Blood Institute Dynamic Registry, patients with COPD (n = 860) and without COPD (n = 10,048) were compared. Baseline demographics, angiographic characteristics, and in-hospital and 1-year adverse events were compared. RESULTS Patients with COPD were older (mean age 66.8 vs 63.2 years, P < .001), more likely to be women, and more likely to have a history of diabetes, prior myocardial infarction, peripheral arterial disease, renal disease, and smoking. Patients with COPD also had a lower mean ejection fraction (49.1% vs 53.0%, P < .001) and a greater mean number of significant lesions (3.2 vs 3.0, P = .006). Rates of in-hospital death (2.2% vs 1.1%, P = .003) and major entry site complications (6.6% vs 4.2%, P < .001) were higher in pulmonary patients. At discharge, pulmonary patients were significantly less likely to be prescribed aspirin (92.4% vs 95.3%, P < .001), β-blockers (55.7% vs 76.2%, P < .001), and statins (60.0% vs 66.8%, P < .001). After adjustment, patients with COPD had significantly increased risk of death (hazard ratio [HR] = 1.30, 95% CI = 1.01-1.67) and repeat revascularization (HR = 1.22, 95% CI = 1.02-1.46) at 1 year, compared with patients without COPD. CONCLUSIONS COPD is associated with higher mortality rates and repeat revascularization within 1 year after PCI. These higher rates of adverse outcomes may be associated with lower rates of guideline-recommended class 1 medications prescribed at discharge.

Impact of drug-eluting stents among insulin-treated diabetic patients: a report from the National Heart, Lung, and Blood Institute Dynamic Registry.

OBJECTIVES This study sought to evaluate the safety and efficacy of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients with insulin- and noninsulin-treated diabetes. BACKGROUND Diabetes is a powerful predictor of adverse events after percutaneous coronary interventions (PCI), and insulin-treated diabetic patients have worse outcomes. The DES are efficacious among patients with diabetes; however, their safety and efficacy, compared with BMS, among insulin-treated versus noninsulin-treated diabetic patients is not well established. METHODS Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 1-year outcomes of insulin-treated (n = 817) and noninsulin-treated (n = 1,749) patients with diabetes who underwent PCI with DES versus BMS. RESULTS The use of DES, compared with BMS, was associated with a lower risk for repeat revascularization for both noninsulin-treated patients (adjusted hazard ratio [HR] = 0.59, 95% confidence interval [CI] 0.45 to 0.76) and insulin-treated subjects (adjusted HR = 0.63, 95% CI 0.44 to 0.90). With respect to safety in the overall diabetic population, DES use was associated with a reduction of death or myocardial infarction (adjusted HR = 0.75, 95% CI 0.58 to 0.96). However, this benefit was confined to the population of noninsulin-treated patients (adjusted HR = 0.57, 95% CI 0.41 to 0.81). Among insulin-treated patients, there was no difference in death or myocardial infarction risk between DES- and BMS-treated patients (adjusted HR = 0.95, 95% CI 0.65 to 1.39). CONCLUSIONS Drug-eluting stents are associated with lower risk for repeat revascularization compared with BMS in treating coronary artery disease among patients with either insulin- or noninsulin-treated diabetes. In addition, DES use is not associated with any significant increased safety risk compared with BMS. These findings suggest that DES should be the preferred strategy for diabetic patients.

Direct Monitoring of Coronary Artery Motion With Cardiac Fat Navigator Echoes

Navigator echoes (NAVs) provide an effective means of monitoring physiological motion in magnetic resonance imaging (MRI). Motion artifacts can be suppressed by adjusting the data acquisition accordingly. The standard pencil‐beam NAV has been used to detect diaphragm motion; however, it does not monitor cardiac motion effectively. Here we report a navigator approach that directly measures coronary artery motion by exciting the surrounding epicardial fat and sampling the signal with a k‐space trajectory sensitized to various motion parameters. The present preliminary human study demonstrates that superior‐inferior (SI) respiratory motion of the coronary arteries detected by the cardiac fat NAV highly correlates with SI diaphragmatic motion detected by the pencil‐beam NAV. In addition, the cardiac fat navigator gating is slightly more effective than the diaphragmatic navigator gating in suppressing motion artifacts in free‐breathing 3D coronary MR angiography (MRA). Magn Reson Med 50:235–241, 2003.