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.

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.

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.

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.

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.

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.

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.

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.

Staphylococcus lugdunensis: a rare but destructive cause of coagulase-negative staphylococcus infective endocarditis.

BACKGROUND: Staphylococcus lugdunensis is a coagulase-negative organism that causes a rare but destructive form of infective endocarditis (IE). We sought to evaluate the clinical and echocardiographic profile of S. lugdunensis IE at our institution and compare it to that of Staphylococcus aureus IE. METHODS: Utilizing microbiology isolates, we retrospectively reviewed cases of S. lugdunensis bacteraemia admitted to our institution between 2002 and 2011 and included cases that met the modified Duke's criteria and those with device infection. We used univariate analysis to compare the clinical and echocardiographic features and outcomes of these patients with 76 cases of S. aureus IE. RESULTS: We identified 15 cases of S. lugdunensis IE (10 native, two prosthetic, three device only), amongst whom five cases had underlying structural valvular heart disease. Echocardiography revealed bulky vegetations in 12, abscesses in three, perforation in four, and valve dehiscence in one case. Overall, 7/12 (58%) of valvular IE involved left-sided valves; six of these underwent successful surgical intervention. S. lugdunensis IE resulted in marked valvular destruction similar to S. aureus IE but was more likely to affect patients with prior structural valvular heart disease (42 vs. 7%, p=0.004). CONCLUSIONS: Unlike other coagulase-negative staphylococci, S. lugdunensis causes a rare but destructive form of IE that can involve structurally normal native valves. Echocardiographic imaging is characterized by bulky vegetations and profound valvular destruction similar to that seen with S. aureus IE, thus isolation of this organism in the blood should not be disregarded as a contaminant. Confirmation of left-sided valvular endocarditis warrants surgical intervention.

Contemporary drug treatment of infective endocarditis.

Infective endocarditis (IE) occurs at a rate of approximately 0.9-6.2 per 100,000 people per year and is associated with a high morbidity and mortality despite advancements in antibiotic and surgical treatments. The general approach to the treatment of IE is initial clinical stabilization, early acquisition of blood cultures, and definitive medical and/or surgical treatment. Surgical consultation should be obtained early when indicated in order to determine the best treatment approach for each individual patient. Surgery is indicated in most cases of prosthetic valve endocarditis, Staphylococcus aureus endocarditis, fungal endocarditis, and endocarditis associated with large vegetations (≥10 mm). Initial antibiotic therapy for IE should be targeted to the culprit microorganism; however, in some cases, empiric therapy must be initiated prior to definitive culture diagnosis. Empiric antibiotics should be targeted toward the most likely pathogens, including staphylococci, streptococci, and enterococci species. Here we discuss the recommended antibiotic regimens for the most common causes of IE as indicated by the American Heart Association and European Society of Cardiology. In 2008, the ACC/AHA published guideline updates on the treatment of valvular heart disease, which included a focused update on endocarditis prophylaxis. According to the most recent guidelines, the number of patients who require antibiotic prophylaxis has decreased substantially. Treatment of IE should be targeted toward the causative microorganism and must be based on the type and location of valve involved (native, prosthetic, left or right sided), the clinical status of the patient, and the likelihood for clinical success. This requires a collaborative effort from multiple medical specialties including infectious disease specialists, cardiologists, and cardiothoracic surgeons.