Recognition and Initial Management of Fulminant Myocarditis: A Scientific Statement From the American Heart Association.

Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe diffuse cardiac inflammation often leading to death resulting from cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Historically, FM was almost exclusively diagnosed at autopsy. By definition, all patients with FM will need some form of inotropic or mechanical circulatory support to maintain end-organ perfusion until transplantation or recovery. Specific subtypes of FM may respond to immunomodulatory therapy in addition to guideline-directed medical care. Despite the increasing availability of circulatory support, orthotopic heart transplantation, and disease-specific treatments, patients with FM experience significant morbidity and mortality as a result of a delay in diagnosis and initiation of circulatory support and lack of appropriately trained specialists to manage the condition. This scientific statement outlines the resources necessary to manage the spectrum of FM, including extracorporeal life support, percutaneous and durable ventricular assist devices, transplantation capabilities, and specialists in advanced heart failure, cardiothoracic surgery, cardiac pathology, immunology, and infectious disease. Education of frontline providers who are most likely to encounter FM first is essential to increase timely access to appropriately resourced facilities, to prevent multiorgan system failure, and to tailor disease-specific therapy as early as possible in the disease process.

How to Manage Temporary Mechanical Circulatory Support Devices in the Critical Care Setting: Translating Physiology to the Bedside.

The incidence of cardiogenic shock and the utilization of mechanical circulatory support devices are increasing in the US. In this review we discuss the pathophysiology of cardiogenic shock through basic hemodynamic and myocardial energetic principles. We also explore the commonly used platforms for temporary mechanical circulatory support, their advantages, disadvantages and practical considerations relating to implementation and management. It is through the translation of underlying physiological principles that we can attempt to maximize the clinical utility of circulatory support devices and improve outcomes in cardiogenic shock.

Predictors and Prognostic Significance of Right Ventricular Ejection Fraction in Patients With Ischemic Cardiomyopathy.

BACKGROUND: Decreased right ventricular (RV) ejection fraction (RVEF) portends poor prognosis in patients with ischemic cardiomyopathy, and previous studies have suggested an association between mitral regurgitation (MR) and RVEF. We sought to evaluate this association and whether mitral valve repair or replacement affects the relationship between RV function and mortality. METHODS: We included 588 patients (mean age, 63±11 years; 75% male) with ischemic cardiomyopathy who underwent cardiac magnetic resonance imaging between 2002 and 2008. Baseline characteristics, left ventricular ejection fraction, MR severity, treatment modality, scar burden, and RVEF were assessed. Multivariable linear regression and Cox proportional hazards models were used to assess the association between MR and RVEF and between RVEF and mortality, respectively. RESULTS: After adjustment for age, sex, left ventricular ejection fraction, right bundle-branch block, and RV scar, MR severity was found to be associated independently with RVEF. There were a total of 240 deaths during a median follow-up time of 5.7 years. After multivariable adjustment, every 10% decrease in RVEF was associated with a 17% increased risk of death (P=0.008). Although decreasing RVEF was associated with a poor prognosis in the nonrepair group (hazard ratio, 1.28; 95% confidence interval, 1.12-1.47; P<0.001), it was not associated with death in the mitral valve repair or replacement group (P for interaction=0.046). CONCLUSIONS: MR severity was found to be an independent predictor of RVEF, as were right bundle-branch block, left ventricular ejection fraction, and the presence of RV scar. Decreasing RVEF is associated with increased mortality in patients with ischemic cardiomyopathy; however, this association may be mitigated in patients who undergo mitral valve repair or replacement.

Clinical predictors of right ventricular dysfunction and association with adverse outcomes in peripartum cardiomyopathy.

AIMS: We sought to identify factors associated with right ventricular (RV) dysfunction and elevated pulmonary artery systolic pressure (PASP) and association with adverse outcomes in peripartum cardiomyopathy (PPCM). METHODS AND RESULTS: We conducted a multi-centre cohort study to identify subjects with PPCM with the following criteria: left ventricular ejection fraction (LVEF) < 40%, development of heart failure within the last month of pregnancy or 5 months of delivery, and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included a composite of (i) major adverse events (need for extracorporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation, or death) or (ii) recurrent heart failure hospitalization. RV function was obtained from echocardiogram reports. In total, 229 women (1993-2017) met criteria for PPCM. Mean age was 32.4 ± 6.8 years, 28% were of African descent, 50 (22%) had RV dysfunction, and 38 (17%) had PASP ≥ 30 mmHg. After a median follow-up of 3.4 years (interquartile range 1.0-8.8), 58 (25%) experienced the composite outcome of adverse events. African descent, family history of cardiomyopathy, LVEF, and PASP were significant predictors of RV dysfunction. Using Cox proportional hazards models, we found that women with RV dysfunction were three times more likely to experience the adverse composite outcome: hazard ratio 3.21 (95% confidence interval: 1.11-9.28), P = 0.03, in a multivariable model adjusting for age, race, body mass index, preeclampsia, hypertension, diabetes, kidney disease, and LVEF. Women with PASP ≥ 30 mmHg had a lower probability of survival free from adverse events (log-rank P = 0.04). CONCLUSIONS: African descent and family history of cardiomyopathy were significant predictors of RV dysfunction. RV dysfunction and elevated PASP were significantly associated with a composite of major adverse cardiac events. This at-risk group may prompt closer monitoring or early referral for advanced therapies.

Risk Factors for Heart Failure Readmission After Cardiac Surgery.

Background: Heart failure (HF) is a leading cause of readmission after cardiac surgery, yet risk factors for HF readmission after cardiac surgery remain poorly characterized. Objectives: This study aimed to identify risk factors associated with 30-day HF-specific readmissions after cardiac surgery using a national database. Methods: We queried the 2016 to 2018 National Readmissions Database to identify U.S. patients who underwent coronary artery bypass grafting (CABG), mitral valve repair/replacement, and/or aortic valve repair/replacement. Exclusion criteria included history of ventricular assist device or heart transplant, dialysis-dependent renal insufficiency, and death during index admission. Clinical variables were defined using International Classification of Diseases-10th Revision codes. The primary outcome was a 30-day readmission for HF following discharge. Multivariable logistic regression was used to account for relevant clinical and demographic covariates and identify independent risk factors for HF readmissions following cardiac surgery. Results: Our study included 394,050 patients who underwent cardiac surgery (mean age 66 ± 12 years, 63% isolated CABG, 27% isolated valve, 11% CABG + valve). Of these patients, 7,318 were readmitted within 30 days of discharge for a principal diagnosis of HF. Independent risk factors of HF-specific readmission included older age, female sex, prolonged length of stay, comorbid congestive HF, nondialysis dependent chronic kidney disease, chronic obstructive pulmonary disease, chronic liver disease, obesity, atrial fibrillation, and acute kidney injury. Prior CABG was marginally protective for HF-specific readmission. Conclusions: Using a national registry, we identified risk factors associated with HF readmission after cardiac surgery. Further analysis of these risk factors and their association with HF readmission is warranted.

Outcomes With Peripheral Venoarterial Extracorporeal Membrane Oxygenation for Suspected Acute Myocarditis: 10-Year Experience From the Extracorporeal Life Support Organization Registry.

BACKGROUND: Acute myocarditis can result in severe hemodynamic compromise requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO). Outcomes and factors associated with mortality among myocarditis patients are not well described in the modern ECMO era. METHODS: We queried the Extracorporeal Life Support Organization registry from 2011 to 2020 for adults with suspected acute myocarditis undergoing peripheral VA-ECMO support. The primary outcome was in-hospital mortality and was compared to all-comers receiving VA-ECMO in the registry over the same period. Secondary outcomes were rates of bridging to advanced therapies and ECMO complications. We used multivariable logistic regression to examine factors associated with in-hospital mortality. RESULTS: Among 850 patients with suspected acute myocarditis receiving peripheral VA-ECMO, the mean age was 41 years, 52% were men, 39% Asian race, and 14.8% underwent extracorporeal cardiopulmonary resuscitation. During the study period, in-hospital mortality steadily declined and was 58.3% for all all-comers receiving VA-ECMO compared with 34.9% for patients with myocarditis (P<0.001). After multivariable modeling, risk factors for mortality were earlier year of support, older age, higher weight, Asian race, need for extracorporeal cardiopulmonary resuscitation, sepsis, and lower mean arterial pressure and pH prior to ECMO initiation. ECMO complications including bleeding, limb ischemia, infections and ischemic stroke were more common among nonsurvivors and significantly declined during the study period. CONCLUSIONS: Compared with all-comers supported with VA-ECMO, in-hospital mortality for patients with acute myocarditis is significantly lower, with nearly two-thirds of patients surviving to discharge. Major modifiable risk factors for mortality were ongoing cardiopulmonary resuscitation requiring ECMO and markers of illness severity prior to ECMO.

Mitral Regurgitation and Mortality Risk in Medicare Beneficiaries With Heart Failure and Preserved Ejection Fraction.

The association of mitral regurgitation (MR) severity and mortality in heart failure with preserved ejection fraction (HFpEF) is uncertain. We sought to evaluate the relation between MR severity on transthoracic echocardiography (TTE) and subsequent all-cause mortality in Medicare beneficiaries with HFpEF. We linked 57,608 patients referred for TTE at Beth Israel Deaconess Medical Center to Medicare inpatient claims from 2003 to 2017. In those with a history of HF and a physician-reported left ventricular ejection fraction ≥50%, we evaluated the relation of MR severity and time to the primary end point of all-cause mortality using Kaplan-Meier methods. A total of 7,778 individuals (14.5%) met inclusion criteria (mean age 75.5 years ± 11.9, 55.9% female). Over a median follow-up of 8.1 years, 2,016 (25.9%) died at a median (interquartile range) of 1.7 (0.3 to 4.1) years. At 1 year, 15.8% with 3 to 4+ MR had died versus 10.5% with 0 to 2+ MR (hazard ratio 1.54, 95% confidence interval 1.22 to 1.95, p <0.001). After multivariable adjustment, 3 to 4+ MR continued to be associated with increased all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.14 to 1.94, p = 0.004) except in the subset with atrial fibrillation (interaction p = 0.03) or recent (<3 months) HF hospitalization (p = 0.54). In conclusion, in this large, single-institution retrospective study of Medicare beneficiaries with HFpEF who underwent TTE, moderate-to-severe and severe MR were significantly associated with an increased risk of all-cause mortality after multivariable adjustment, except in those with atrial fibrillation or recent HF. Prospective studies are needed to assess the role of MR reduction in mitigating this risk.

Cardiogenic shock related cardiovascular disease mortality trends in US population: Heart failure vs. acute myocardial infarction as contributing causes.

BACKGROUND: Observational and trial data have revealed significant improvement in cardiogenic shock (CS) mortality due to acute myocardial infarction (AMI) after introducing early coronary revascularization. Less is known about CS mortality due to heart failure (HF), which is increasingly recognized as a distinct entity from AMI-CS. METHODS AND RESULTS: In this nationwide observational study, the CDC WONDER database was used to identify national trends in age-adjusted mortality rates (AAMR) due to CS (HF vs. AMI related) per 100,000 people aged 35-84. AAMR from AMI-CS decreased significantly from 1999 to 2009 (AAPC: -6.9% [95%CI -7.7, -6.1]) then stabilized from 2009 to 2020. By contrast, HF-CS associated AAMR rose steadily from 2009 to 2020 (AAPC: 13.3% [95%CI 11.4,15.2]). The mortality rate was almost twice as high in males compared to females in both AMI-CS and HF-CS throughout the study period. HF-CS mortality in the non-Hispanic Black population is increasing more quickly than that of the non-Hispanic White population (AAMR in 2020: 4.40 vs. 1.97 in 100,000). The AMI-CS mortality rate has been consistently higher in rural than urban areas (30% higher in 1999 and 28% higher in 2020). CONCLUSIONS: These trends highlight the fact that HF-CS and AMI-CS represent distinct clinical entities. While mortality associated with AMI-CS has primarily declined over the last two decades, the mortality related to HF-CS has increased significantly, particularly over the last decade, and is increasing rapidly among individuals younger than 65. Accordingly, a dramatic change in the demographics of CS patients in modern intensive care units is expected.

NT-proBNP and predictors of event free survival and left ventricular systolic function recovery in peripartum cardiomyopathy.

OBJECTIVE: To determine predictors of adverse outcomes in peripartum cardiomyopathy (PPCM). METHODS AND RESULTS: We conducted a multi-center cohort study across four centers to identify subjects with PPCM with the following criteria: LVEF <40%, development of heart failure within the last month of pregnancy or within 5 months of delivery and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included 1) survival free from major adverse events (need for extra-corporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation or death) and 2) LVEF recovery ≥ 50%. Using a univariate logistic regression analysis, we identified significant clinical predictors of these outcomes, which were then used to create multivariable models. NT-proBNP at the time of diagnosis was examined both as a continuous variable (log transformed) in logistic regression and as a dichotomous variable (values above and below the median) using the log-rank test. In all, 237 women (1993 to 2017) with 736.4 person-years of follow-up, met criteria for PPCM. Participants had a mean age of 32.4 ± 6.7 years, mean BMI 30.6 ± 7.8 kg/m2; 63% were White. After median follow-up of 3.6 years (IQR 1.1-7.8), 113 (67%) had LVEF recovery, and 222 (94%) had survival free from adverse events. Significant predictors included gestational age, gravidity, systolic blood pressure, smoking, heart rate, initial LVEF, and diuretic use. In a subset of 110 patients with measured NTproBNP levels, we found a higher event free survival for women with NTproBNP <2585 pg/ml (median) as compared to women with NTproBNP ≥2585 pg/ml (log-rank test p-value 0.018). CONCLUSION: Gestational age, gravidity, current or past tobacco use, systolic blood pressure, heart rate, initial LVEF and diuretic requirement at the time of diagnosis were associated with survival free from adverse events and LVEF recovery. Initial NT-proBNP was significantly associated with event free survival.

Fulminant cardiac sarcoidosis resembling giant cell myocarditis: a case report.

BACKGROUND: Severe cardiac sarcoidosis (CS) can share clinical and histopathologic features with giant cell myocarditis (GCM). CASE SUMMARY: A 56-year-old female presented with 1 week of exertional chest pressure and dyspnoea. Echocardiogram demonstrated extensive regional dysfunction with left ventricular ejection fraction (LVEF) 38%. Cardiac catheterization revealed no obstructive coronary artery disease and cardiac index 1.5 L/min/m2. Cardiac magnetic resonance imaging (MRI) demonstrated diffuse late gadolinium enhancement. Positron emission tomography with fluorodeoxyglucose (FDG) (FDG-PET) computed tomography showed FDG uptake in the anteroseptal and anterior wall and no extracardiac activity. Endomyocardial biopsy (EMB) demonstrated fragments of endocardial fibrosis with mixed inflammatory infiltrate including histiocytic giant cells, which could be due to CS or GCM. She was initially treated for GCM with high dose steroids, tacrolimus, and mycophenolate mofetil. Repeat EMB was pursued and demonstrated multiple granulomas with sharp demarcation from adjacent uninvolved myocardium consistent with CS. A dual-chamber implantable cardioverter-defibrillator was placed, and immunosuppression was changed to prednisone alone with plan for infliximab. DISCUSSION: This case illustrates a rare presentation of fulminant isolated CS. Endomyocardial biopsy with sufficient tissue was critical to establish a diagnosis and initiate appropriate immunosuppression.

Arrhythmia in Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is a complex disease that can manifest as a diverse array of arrhythmias. CS patients may be at higher risk for sudden cardiac death (SCD), and, in some cases, SCD may be the first presenting symptom of the underlying disease. As such, identification, risk stratification, and management of CS-related arrhythmia are crucial in the care of these patients. Left untreated, CS carries significant arrhythmogenic morbidity and mortality. Cardiac manifestations of CS are a consequence of an inflammatory process resulting in the myocardial deposition of noncaseating granulomas. Endomyocardial biopsy remains the gold standard for diagnosis; however, biopsy yield is limited by the patchy distribution of the granulomas. As such, recent guidelines have improved clinical diagnostic pathways relying on advanced cardiac imaging to help in the diagnosis of CS. To date, corticosteroids are the best studied agent to treat CS but are associated with significant risks and limited benefits. Implantable cardioverter-defibrillators have an important role in SCD risk reduction. Catheter ablation in conjunction with antiarrhythmics seems to reduce ventricular arrhythmia burden. However, the appropriate selection of these patients is crucial as ablation is likely more helpful in the setting of a myocardial scar substrate versus arrhythmia driven by active inflammation. Further studies investigating CS pathophysiology, the pathway to diagnosis, arrhythmogenic manifestations, and SCD risk stratification will be crucial to reduce the high morbidity and mortality of this disease.

Safety and Effectiveness of an Accelerated Intravenous Iron Administration Protocol in Hospitalized Patients With Heart Failure.

BACKGROUND: The ACC/AHA heart failure (HF) guidelines include a class IIb recommendation for intravenous (IV) iron replacement in patients with iron deficiency and New York Heart Association class II or III to improve functional status and quality of life. Several studies have addressed the use of IV iron formulations such as ferric carboxymaltose or iron sucrose in HF population; however, few studies focused on sodium ferric gluconate complex (SFGC). OBJECTIVES: To assess the safety and effectiveness of an IV SFGC administration protocol in patients hospitalized with HF. METHODS: A retrospective cohort study was conducted. We included patients admitted to the HF service from September 2017 to March 2018. The primary outcome was the frequency of adverse reactions. The secondary outcome was the odds of HF readmissions between the 2 groups (IV SFGC vs. control). RESULTS: Of the 123 patients, 70 received IV iron (SFGC group) and 53 did not receive IV iron (control group). Five (7%) patients of the 70 in the SFGC group experienced adverse events, which included hypotension (n = 2, 2.8%), fever (n = 2, 2.8%) and myalgia (n = 2, 2.8%). Nine (12.8%) and 18 (25.7%) were readmitted within 30 days and 6 months respectively. In the control arm, 5 (9.4%) and 14 (26.4%) were admitted within 30 days and 6 months respectively. The odds of HF readmission at 30 days [OR 1.4 (95% CI: 0.45, 4.5)] and at 6 months [OR 0.96 (95% CI: 0.43, 2.2)] were similar in those who did not receive IV iron compared to those who received IV iron. CONCLUSIONS: Sodium ferric gluconate complex given at an accelerated dosing schedule appears to provide a more efficient means to prescribe IV iron in the inpatient setting and is safe with a low frequency of hypotension, fevers, and myalgias.

Umbilical cord blood-selected CD133(+) cells exhibit vasculogenic functionality in vitro and in vivo.

BACKGROUND AIMS: Current clinical trials utilize non-selected bone marrow (BM) mononuclear cells (MNC) to augment vasculo genesis within ischemic vascular beds. Recent reports have identified a diminished number and function of hemat-opoietic stem cells (HSC) from aged and diseased patients. Umbilical cord blood (UCB) provides a potential robust allo-geneic source of HSC for therapeutic vasculogenesis. METHODS: MNC and magnetically isolated CD133(+) cells were assessed for viability (trypan blue) and surface phenotype (flow cytometry). To test in vivo functionality of the cells, NOD/SCID mice underwent ligation of the right femoral artery followed immediately by cell injection. Blood flow recovery, necrosis, BM engraftment of human cells and histologic capillary density were determined. Cells were tested for potential mechanisms mediating the in vivo effects, including migration, cytokine secretion and angiogenic augmentation (Matrigel assays). RESULTS: Surface expression analysis showed CD31 (PECAM) expression was greatly increased in UCB CD133(+) cells compared with BM MNC. At 28 days, perfusion ratios were highest in animals receiving UCB CD133(+) cells, while animals receiving BM CD133(+) cells and BM MNC demonstrated perfusion ratios statistically higher than in animals treated with cytokine media alone. Animals receiving CD133(+) cells showed a statistically higher capillary density, reduced severe digit necrosis and increased engraftment in the BM than animals treated with unselected BM MNC. In vitro studies showed equivalent migration to stromal-derived factor-1 (SDF-1), increased production of tumor necrosis factor alpha (TNF-alpha) and increased branch points with the co-incubation of CD133(+) cells with human umbilical vein endothelial cells (HUVEC) in the Matrigel angiogenesis assay. CONCLUSIONS: Taken together, UCB CD133(+) cells exhibit robust vasculogenic functionality compared with BM MNC in response to ischemia.

Massive retroperitoneal hemorrhage after external shock wave lithotripsy in a patient with a left ventricular assist device.

As left ventricular assist devices (LVADs) become more prevalent, it is increasingly likely that patients with LVADs will require non cardiac procedures. Peri-procedural anticoagulation management is challenging in these patients and requires balancing risks of bleeding and pump thrombosis. We present a case of a patient with a HeartWare LVAD who developed a massive retroperitoneal hemorrhage after external shock wave lithotripsy (ESWL) for an obstructing renal calculus and briefly review the literature regarding bleeding complications after ESWL as well as peri-procedural anticoagulation management of patients with LVADs.

Retrospective evaluation of echocardiographic variables for prediction of heart failure hospitalization in heart failure with preserved versus reduced ejection fraction: A single center experience.

BACKGROUND: Limited data exist on the differential ability of variables on transthoracic echocardiogram (TTE) to predict heart failure (HF) readmission across the spectrum of left ventricular (LV) systolic function. METHODS: We linked 15 years of TTE report data (1/6/2003-5/3/2018) at Beth Israel Deaconess Medical Center to complete Medicare claims. In those with recent HF, we evaluated the relationship between variables on baseline TTE and HF readmission, stratified by LVEF. RESULTS: After excluding TTEs with uninterpretable diastology, 5,900 individuals (mean age: 76.9 years; 49.1% female) were included, of which 2545 individuals (41.6%) were admitted for HF. Diastolic variables augmented prediction compared to demographics, comorbidities, and echocardiographic structural variables (p < 0.001), though discrimination was modest (c-statistic = 0.63). LV dimensions and eccentric hypertrophy predicted HF in HF with reduced (HFrEF) but not preserved (HFpEF) systolic function, whereas LV wall thickness, NT-proBNP, pulmonary vein D- and Ar-wave velocities, and atrial dimensions predicted HF in HFpEF but not HFrEF (all interaction p < 0.10). Prediction of HF readmission was not different in HFpEF and HFrEF (p = 0.93). CONCLUSIONS: In this single-center echocardiographic study linked to Medicare claims, left ventricular dimensions and eccentric hypertrophy predicted HF readmission in HFrEF but not HFpEF and left ventricular wall thickness predicted HF readmission in HFpEF but not HFrEF. Regardless of LVEF, diastolic variables augmented prediction of HF readmission compared to echocardiographic structural variables, demographics, and comorbidities alone. The additional role of medication adherence, readmission history, and functional status in differential prediction of HF readmission by LVEF category should be considered for future study.

Antibody-mediated rejection 16 years post-cardiac transplantation: a case report of an uncommon late presentation in a middle-aged woman.

BACKGROUND: Very late antibody-mediated rejection (AMR) in heart transplant patients (over 10 years post-transplant) is very rare. It is associated with high mortality, graft dysfunction, and fulminant coronary artery vasculopathy (CAV) and should remain in the differential for patients presenting with late graft dysfunction. CASE SUMMARY: A 57-year-old woman 16 years of post-heart transplant with a previously unremarkable post-transplant course including protocol driven biopsies showing no rejection and a recent unremarkable screening nuclear stress test presented to our institution with clinical heart failure. Echocardiogram revealed graft dysfunction and endomyocardial biopsy showed no signs of cellular rejection, but evidence of AMR. The patient was treated with steroid and immunotherapy with clinical improvement but suffered several infectious complications and renal dysfunction requiring haemodialysis related to her immunotherapy treatment. Despite aggressive AMR management, donor-specific antibodies and symptoms persisted and CAV progressed. DISCUSSION: This case illustrates the poor diagnostic yield of non-invasive testing for AMR, and highlights importance to clinicians of considering AMR even if the patient over 10 years post-transplant when the diagnosis is rare.

Coronary Artery Disease Is a Predictor of Progression to Dialysis in Patients With Chronic Kidney Disease, Type 2 Diabetes Mellitus, and Anemia: An Analysis of the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).

BACKGROUND: Although clear evidence shows that chronic kidney disease is a predictor of cardiovascular events, death, and accelerated coronary artery disease (CAD) progression, it remains unknown whether CAD is a predictor of progression of chronic kidney disease to end-stage renal disease. We sought to assess whether CAD adds prognostic information to established predictors of progression to dialysis in patients with chronic kidney disease, diabetes, and anemia. METHODS AND RESULTS: Using the previously described Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) population, we compared baseline characteristics of patients with and without CAD. Cox proportional hazards models were used to assess the association between CAD and the outcomes of end-stage renal disease and the composite of death or end-stage renal disease. Of the 4038 patients, 1791 had a history of known CAD. These patients were older (mean age 70 versus 65 years, P<0.001) and more likely to have other cardiovascular disease. CAD patients were less likely to have marked proteinuria (29% versus 39%, P<0.001), but there was no significant difference in estimated glomerular filtration rate between the 2 groups. After adjusting for age, sex, race, estimated glomerular filtration rate, proteinuria, treatment group, and 14 other renal risk factors, patients with CAD were significantly more likely to progress to end-stage renal disease (adjusted hazard ratio 1.20 [95% CI 1.01-1.42], P=0.04) and to have the composite of death or end-stage renal disease (adjusted hazard ratio 1.15 [95% CI 1.01-1.30], P=0.03). CONCLUSIONS: In patients with chronic kidney disease, diabetes, and anemia, a history of CAD is an independent predictor of progression to dialysis. In patients with diabetic nephropathy, a history of CAD contributes important prognostic information to traditional risk factors for worsening renal disease.

A new class of drugs for systolic heart failure: The PARADIGM-HF study.

The PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) found a combination drug containing sacubitril (a neprilysin inhibitor) and valsartan (an angiotensin II receptor blocker) superior to enalapril (an angiotensin-converting enzyme inhibitor) in patients with systolic heart failure. Recently approved by the US Food and Drug Administration, sacubitril-valsartan is the first new drug in over a decade to decrease death rates in patients with systolic heart failure.