Cardiotoxicity among socioeconomically marginalized breast cancer patients.

PURPOSE: Evidence of cardiotoxicity risk related to anthracycline or trastuzumab exposure is largely derived from breast cancer cohorts that under-represent socioeconomically marginalized women, who may be at increased risk of cardiotoxicity because of high prevalence of cardiovascular disease risk factors. Therefore, we aimed to estimate cardiotoxicity risk among socioeconomically marginalized breast cancer patients treated with anthracyclines or trastuzumab and describe clinical consequences of cardiotoxicity. METHODS: We linked electronic health records with institutional registry data from a Comprehensive Community Cancer Program within a safety-net health system. Eligible patients were adult females, diagnosed with first primary invasive breast cancer between 2013 and 2017, and initiated anthracyclines or trastuzumab as part of first-line therapy. We estimated cumulative incidence (risk) of cardiotoxicity with corresponding 95% confidence limits (CL) using the Aalen-Johansen estimator with death as competing risk. RESULTS: Our study population comprised 169 women with breast cancer (103 initiated anthracyclines and 66 initiated trastuzumab). Cumulative incidence of cardiotoxicity was 21% (95% CL: 12%, 32%) at one year and 25% (95% CL: 15%, 35%) at three years among women who initiated trastuzumab, whereas cumulative incidence was 3.9% (95% CL: 1.3%, 8.9%) at one year and 5.9% (95% CL: 2.4%, 12%) at three years among women who initiated anthracyclines. More than half of patients with cardiotoxicity experienced interruption of cancer treatment. CONCLUSION: Our findings suggest high risk of cardiotoxicity among socioeconomically marginalized breast cancer patients after initiation of anthracyclines or trastuzumab. Strategies are needed for optimizing cancer treatment effectiveness while minimizing cardiotoxicity in this population.

Does the Society of Thoracic Surgeons risk score accurately predict operative mortality for patients with pulmonary hypertension?

OBJECTIVE: This study assessed the impact of pulmonary hypertension (PH) on morbidity and mortality after the most common cardiac operations and evaluated the accuracy of the Society of Thoracic Surgeons (STS) risk model for patients with PH. METHODS: At a single center between 1994 and 2010, all adult cardiac operations performed with recorded preoperative mean pulmonary arterial pressure (MPAP) and STS predicted mortality were reviewed. MPAP was defined as normal (<25 mm Hg) or as mild (25-34 mm Hg), moderate (35-44 mm Hg), or severe (≥ 45 mm Hg) PH. Multivariate analysis was performed to elucidate the contribution of PH to morbidity and mortality. RESULTS: In all, 3343 patient records were reviewed. Coronary artery bypass grafting (CABG) was the most common procedure (67.5%), followed by aortic valve replacement (24.9%) and mitral valve procedures (6.3%). Postoperative complications and mortality increased with increasing MPAP. Multivariable analysis found that both moderate (odds ratio, 7.17; P < .001) and severe (odds ratio, 13.73; P < .001) PH were significantly associated with increased mortality, even after accounting for STS risk. A subset analysis of isolated CABG cases revealed markedly increased mortality for all categories of PH (mild odds ratio, 1.99; moderate odds ratio, 11.5; severe odds ratio, 38.9; P < .001). CONCLUSIONS: Morbidity and mortality were independently associated with PH. Observed mortality was significantly higher than predicted by the STS model for patients with moderate and severe PH, particularly in isolated CABG. Addition of PH to the STS risk model should be considered, or alternative tools should be used to assess risk in these patients.

Increasing lead burden correlates with externalized cables during systematic fluoroscopic screening of Riata leads.

PURPOSE: Riata and Riata ST defibrillator leads (St. Jude Medical, Sylmar, CA, USA) have been recalled due to increased risk of insulation failure leading to externalized cables. As this mechanical failure does not necessarily correlate with electrical failure, it can be difficult to diagnose. Fluoroscopic screening can identify insulation failure. Studies have suggested that insulation failure is predominantly seen in 8-Fr, single-coil models. Our patients have exclusively dual-coil leads and a high proportion of 7-Fr leads. METHODS: Fluoroscopic screening was performed in 48 patients with recalled Riata leads. Twenty-three patients had 8-Fr Riata leads and 25 patients had 7-Fr Riata ST leads. Images were recorded in at least three projections and studies were reviewed by seven attending electrophysiologists. RESULTS: Externalized cables were seen in ten patients (21 %), and another five patients (10 %) had abnormal cable spacing. All device interrogations showed normal parameters. Patients with abnormal leads had more leads in situ (2.5 ± 0.7 vs. 1.6 ± 0.8 leads; P = 0.002) and a higher rate of nonischemic cardiomyopathy (80 vs. 24 %; P = 0.03). There were no differences between the groups with regards to patient age, body mass index, lead age, lead parameters, or vascular access site. There was no difference with regard to lead size (P = 0.76). CONCLUSIONS: The Riata family of leads has a high incidence of mechanical failure, as demonstrated on fluoroscopic screening. In this study, the 7-Fr models were just as likely to mechanically fail as the 8-Fr models. Increasing lead burden and a diagnosis of nonischemic cardiomyopathy correlated with insulation failure.

Prediction of mortality in clinical practice for medicare patients undergoing defibrillator implantation for primary prevention of sudden cardiac death.

OBJECTIVES: The aim of this study was to derive and validate a practical risk model to predict death within 4 years of primary prevention implantable cardioverter-defibrillator (ICD) implantation. BACKGROUND: ICDs for the primary prevention of sudden cardiac death improve survival, but recent data suggest that a patient subset with high mortality and minimal ICD benefit may be identified. METHODS: Data from a development cohort (n = 17,991) and validation cohort (n = 27,893) of Medicare beneficiaries receiving primary prevention ICDs from 2005 to 2007 were merged with outcomes data through mid-2010 to construct and validate complete and abbreviated risk models for all-cause mortality using Cox proportional hazards regression. RESULTS: Over a median follow-up period of 4 years, 6,741 (37.5%) development and 8,595 (30.8%) validation cohort patients died. The abbreviated model was based on 7 clinically relevant predictors of mortality identified from complete model results, referred to as the "SHOCKED" predictors: 75 years of age or older (hazard ratio [HR]: 1.70; 95% confidence interval [CI]: 1.62 to 1.79), heart failure (New York Heart Association functional class III) (HR: 1.35; 95% CI: 1.29 to 1.42), out of rhythm because of atrial fibrillation (HR: 1.26; 95% CI: 1.19 to 1.33), chronic obstructive pulmonary disease (HR: 1.70; 95% CI: 1.61 to 1.80), kidney disease (chronic) (HR: 2.33; 95% CI: 2.20 to 2.47), ejection fraction (left ventricular) ≤ 20% (HR: 1.26; 95% CI: 1.20 to 1.33), and diabetes mellitus (HR: 1.43; 95% CI: 1.36 to 1.50). This model had C-statistics of 0.75 (95% CI: 0.75 to 0.76) and 0.74 (95% CI: 0.74 to 0.75) in the development and validation cohorts, respectively. Validation patients in the highest risk decile on the basis of the SHOCKED predictors had a 65% 3-year mortality rate. A nomogram is provided for survival probabilities 1 to 4 years after ICD implantation. CONCLUSIONS: This useful model, based on more than 45,000 primary prevention ICD patients, accurately identifies patients at highest risk for death after device implantation and may significantly influence clinical decision making.

Initial experience of sequential surgical epicardial-catheter endocardial ablation for persistent and long-standing persistent atrial fibrillation with long-term follow-up.

BACKGROUND: Patients with long-standing persistent (LSP) atrial fibrillation (AF) who have previously undergone catheter ablation represent a challenging patient population. Repeat catheter ablation in these patients is arduous and associated with a high failure rate, whereas surgical ablation can be complicated by multiple flutters. We sought to determine if minimally-invasive surgical ablation, followed by catheter ablation of all inducible flutters, would improve success rates over repeat catheter ablation alone. METHODS: Fifteen patients (Sequential) with persistent or LSP AF who failed at least one catheter ablation and one anti-arrhythmic drug (AAD) underwent surgical ablation, followed by planned endocardial evaluation and catheter mapping with ablation during the same hospitalization. Sequential patients were matched to 30 patients who had previously failed at least one catheter ablation and underwent a repeat catheter ablation (catheter-alone). The primary end point was event-free survival of any documented AF recurrence or AAD use. RESULTS: All patients underwent uncomplicated surgical ablation and electrophysiology procedure. Five Sequential patients had seven inducible flutters that were mapped and ablated. After a mean follow-up of 20.7±4.5 months, 13/15 (86.7%) Sequential patients, but only 16/30 (53.3%) catheter-alone patients, were free of any atrial arrhythmia and off of AAD (p=0.04). On AAD, 14/15 (93.3%) Sequential patients were free of any atrial arrhythmia recurrence, compared to 17/30 (56.7%) catheter-alone patients (p=0.01). CONCLUSIONS: For patients with atrial fibrillation who have failed catheter ablation, Sequential minimally invasive epicardial surgical ablation, followed by endocardial catheter-based ablation, has a higher early success rate than repeat catheter ablation alone.

Incidence, risk factors, and consequences of new-onset atrial fibrillation following epicardial ablation for ventricular tachycardia.

INTRODUCTION: We sought to determine the incidence, predictors, and consequences of new-onset atrial fibrillation (AF) following epicardial ventricular tachycardia (VT) ablation. METHODS AND RESULTS: A total of 41 patients with no prior history of AF underwent epicardial VT ablation via a percutaneous subxiphoid approach. All patients were monitored continuously for 3 days following ablation and then via implantable cardiac defibrillator (ICD) or Holter monitoring. Mean age was 70.0 ± 11.3 years and mean ejection fraction was 30.3 ± 16.6%. In seven (17%) patients, the right ventricle (RV) was punctured during access with subsequent needle withdrawal without requiring surgical repair. Thirty patients (73%) were treated with amiodarone following ablation. Post-ablation, eight (19.5%) patients had documented new-onset AF within 7 days. All AF patients had clinical symptoms of pericarditis. One patient with AF was maintained on amiodarone post-procedure. Complications of AF included three patients who received inappropriate ICD shocks and one patient who developed a large, left atrial appendage clot. Acutely, all patients responded to short-term medical therapy or electrical cardioversion. At 18.0 ± 9.0 months of follow-up, no patient had recurrence of AF, and all were off antiarrhythmic drugs. One patient had typical atrial flutter requiring catheter ablation. Risk factors for AF included lack of amiodarone immediately after ablation (12.5 vs. 87.9%, P < 0.001), RV puncture (50.0 vs. 9.1%, P = 0.02), and epicardial ablation time >10 min (62.5 vs. 3.0%, P < 0.001). CONCLUSIONS: Atrial fibrillation after epicardial ablation is common and can lead to ICD shocks and atrial thrombus formation. Short-term antiarrhythmic drug therapy and ICD reprogramming should be considered after epicardial VT ablation.

The role of ultrafiltration in patients with decompensated heart failure.

Congestion, due in large part to hypervolemia, is the primary driver of heart failure (HF) admissions. Relief of congestion has been traditionally achieved through the use of loop diuretics, but there is increasing concern that these agents, particularly at high doses, may be deleterious in the inpatient setting. In addition, patients with HF and the cardiorenal syndrome (CRS) have diminished response to loop diuretics, making these agents less effective at relieving congestion. Ultrafiltration, a mechanical volume removal strategy, has demonstrated promise in achieving safe and effective volume removal in patients with cardiorenal syndrome and diuretic refractoriness. This paper outlines the rationale for ultrafiltration in CRS and the available evidence regarding its use in patients with HF. At present, the utility of ultrafiltration is restricted to selected populations, but a greater understanding of how this technology impacts HF and CRS may expand its use.

Bundle-branch block morphology and other predictors of outcome after cardiac resynchronization therapy in Medicare patients.

BACKGROUND: Clinical trials of cardiac resynchronization therapy (CRT) have enrolled a select group of patients, with few patients in subgroups such as right bundle-branch block (RBBB). Analysis of population-based outcomes provides a method to identify real-world predictors of CRT outcomes. METHODS AND RESULTS: Medicare Implantable Cardioverter-Defibrillator Registry (2005 to 2006) data were merged with patient outcomes data. Cox proportional-hazards models assessed death and death/heart failure hospitalization outcomes in patients with CRT and an implantable cardioverter-defibrillator (CRT-D). The 14 946 registry patients with CRT-D (median follow-up, 40 months) had 1-year, 3-year, and overall mortality rates of 12%, 32%, and 37%, respectively. New York Heart Association class IV heart failure status (1-year hazard ratio [HR], 2.23; 3-year HR, 1.98; P<0.001) and age ≥ 80 years (1-year HR, 1.74; 3-year HR, 1.75; P<0.001) were associated with increased mortality both early and late after CRT-D. RBBB (1-year HR, 1.44; 3-year HR, 1.37; P<0.001) and ischemic cardiomyopathy (1-year HR, 1.39; 3-year HR, 1.44; P<0.001) were the next strongest adjusted predictors of both early and late mortality. RBBB and ischemic cardiomyopathy together had twice the adjusted hazard for death (HR, 1.99; P<0.001) as left BBB and nonischemic cardiomyopathy. QRS duration of at least 150 ms predicted more favorable outcomes in left BBB but had no impact in RBBB. A secondary analysis showed lower hazards for CRT-D compared with standard implantable cardioverter-defibrillators in left BBB compared with RBBB. CONCLUSIONS: In Medicare patients, RBBB, ischemic cardiomyopathy, New York Heart Association class IV status, and advanced age were powerful adjusted predictors of poor outcome after CRT-D. Real-world mortality rates 3 to 4 years after CRT-D appear higher than previously recognized.

Nail-patella syndrome with an emphasis on the risk of renal and ocular findings.

We describe a 6-year-old girl presenting with nail dysplasia affecting all nails and hands for 2 years. Changes were seen on the ulnar side of the nails. She was assessed for limitation of elbow movements at 3 weeks of age and underwent physiotherapy for thickened biceps tendon. She subsequently developed laxity of knees and ankles, and x-ray revealed absent patellae at 32 weeks. She had behavioral abnormalities and sleep disturbances. X-ray of the pelvis revealed iliac horns, and urinalysis showed 3+ proteinuria. She had mixed hyperlipidemia. Her chromosomal analysis was normal but showed a mutation in the LMX1B gene. She was diagnosed to have Nail-patella syndrome or Hereditary osteo-onychodysplasia (HOOD Syndrome). Her renal imaging was normal, as were her ocular pressures. She is under regular surveillance by a multi-disciplinary team of genetic counselors, orthopedists, rheumatologists and ophthalmologists. She is currently prescribed enalapril, melatonin and simvastatin.

Correlation of impedance cardiography with invasive hemodynamic measurements in patients with advanced heart failure: the BioImpedance CardioGraphy (BIG) substudy of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) Trial.

BACKGROUND: Impedance cardiography (ICG) is a noninvasive modality that uses changes in impedance across the thorax to assess hemodynamic parameters, including cardiac output (CO). The utility of ICG in patients hospitalized with heart failure is uncertain. METHODS: The BioImpedance CardioGraphy in Advanced Heart Failure study was a prospective substudy of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness. A total of 170 subjects underwent blinded ICG measurements using BioZ (CardioDynamics, San Diego, CA); of these, 82 underwent right heart catheterization. We compared ICG with invasively measured hemodynamics by simple correlation and compared overall ICG hemodynamic profiles ("wet" [thoracic fluid content > or =47/kOhm in men and > or =37/kOhm in women] and "cold" [cardiac index < or =2.2 L min(-1)m(-2)) versus those determined by invasive measurements (wet [pulmonary capillary wedge pressure > or =22 mm Hg] and cold [cardiac index < or =2.2 L min(-1)m(-2)). We also determined whether ICG measurements were associated with subsequent death or hospitalization within 6 months. RESULTS: There was modest correlation between ICG and invasively measured CO (r = 0.4 to 0.6 on serial measurement). Thoracic fluid content measured by ICG was not a reliable measure of pulmonary capillary wedge pressure. There was poor agreement between ICG and invasively measured hemodynamic profiles (kappa < or =0.1). No ICG variable alone or in combination was associated with outcome. CONCLUSIONS: In hospitalized patients with advanced heart failure, ICG provides some information about CO but not left-sided filling pressures. Impedance cardiography did not have prognostic utility in this patient population.

Characteristics and outcomes in African American patients with decompensated heart failure.

BACKGROUND: Outcomes in patients with chronic heart failure vary by race. Racial differences in the characteristics and outcomes of patients with acute decompensated heart failure (ADHF) have not been well characterized. Therefore, we assessed race-related differences in presentation, treatment, in-patient experiences, and short-term mortality due to ADHF before and after accounting for known covariates. METHODS: The Acute Decompensated Heart Failure National Registry database was analyzed to evaluate demographic and mortality differences in African American and white patients with ADHF entered into the database from its initiation in September 2001 to December 31, 2004. Stratified analyses by cause, age, left ventricular function, and history of heart failure subgroups were also conducted. RESULTS: A total of 105,872 episodes of ADHF occurred in white patients and 29,862 occurred in African American patients. African American patients with ADHF were younger than white patients (mean [SD] age, 63.5 [15.4] vs 72.5 [12.5] years) and had lower mean left ventricular ejection fractions. The prevalence of hypertension, diabetes mellitus, and obesity was higher in African American patients. African American race was associated with lower in-hospital mortality after adjustment for known predictors (2.1% vs 4.5%; adjusted odds ratio [OR], 0.79; 95% confidence interval [CI], 0.72-0.87; P < .001). This association persisted for all age cohorts, was independent of the use of intravenous vasoactive drugs, and was especially present in African American patients in the nonischemic subgroup (adjusted OR, 0.74; 95% CI, 0.57-0.96) but not the ischemic subgroup (adjusted OR, 0.91; 95% CI, 0.76-1.09). CONCLUSION: In ADHF, African American race is associated with lower in-hospital mortality compared with white race, despite certain indicators of increased disease severity.

Sex differences in the association between leptin and CRP: results from the Dallas Heart Study.

OBJECTIVE: Higher C-reactive protein (CRP) levels in women compared with men may reflect sex differences in the relationship between obesity and inflammation. We evaluated how the adipokine leptin influenced these relationships. METHODS AND RESULTS: Dual energy X-ray absorptometry measurements of fat mass and plasma levels of leptin and CRP were measured in 1188 women and 1102 men from the Dallas Heart Study. Analyses were stratified by sex and a leptin/percent fat index was created to evaluate the association between leptin and CRP independent of fat mass. Women had higher body mass index, percent fat mass, and plasma levels of CRP and leptin. CRP levels correlated with leptin levels in both women (Spearman rho=0.48, p<0.0001) and in men (rho=0.27, p<0.0001). In multivariable models adjusting for confounders including total fat mass, leptin/percent fat index remained significantly associated with logCRP in women (p=0.005), but not in men (p=0.95). A significant interaction was observed between sex and leptin levels on CRP (p(interaction)=0.03). CONCLUSION: Leptin was associated with CRP independent of other measures of obesity in women, but not in men. These findings suggest that sex differences in CRP may reflect sex-related differences in the inflammatory responses to obesity, and may in part, be mediated by leptin.

Increased prevalence of concentric left ventricular hypertrophy in African-Americans: will an epidemic of heart failure follow?

Left ventricular hypertrophy (LVH), used in this review to denote abnormally increased left ventricular (LV) mass, is an important cardiac trait because of its association with numerous adverse cardiovascular outcomes including myocardial infarction and heart failure. LV mass is typically assessed by noninvasive cardiac imaging (echocardiography or MRI); electrocardiography is an insensitive measure. There are two predominant types of hypertrophy: concentric, where LV wall thickness is increased relative to cavity dimensions, and eccentric, where LV wall thickness is not increased relative to cavity dimensions. Several large studies indicate that the prevalence of concentric LVH is higher in African-Americans versus whites. Although there are data to suggest that concentric LVH results in systolic heart failure in animal models, such data are lacking in humans. How concentric LVH affects the prevalence of systolic and diastolic heart failure in African-Americans needs further study. Given the large burden of LVH among African-Americans, such data are needed to estimate the expected burden and type of heart failure which will occur in the future in this population.

Low voltage on the electrocardiogram is a marker of disease severity and a risk factor for adverse outcomes in patients with heart failure due to systolic dysfunction.

BACKGROUND: The prognostic implications of low QRS voltage on the electrocardiogram (ECG) in heart failure (HF) are not well characterized. METHODS: We manually measured and summed the QRS voltage in all 12 leads of the ECG (sumQRS) in two cohorts: (1) 415 patients with a low left ventricular ejection fraction followed up in a HF clinic ("clinic cohort") and (2) 100 subjects with advanced HF who had an ECG within 1 year preceding cardiac transplantation ("pretransplant cohort"). Low voltage was defined as the lowest quartile of the clinic cohort (sumQRS <12 mV) and its prevalence was compared in the two cohorts. The associations of low voltage with 1-year outcomes were assessed in the clinic cohort. RESULTS: In the clinic cohort, the frequency of low voltage was higher in New York Heart Association class 4 versus class 1-3 patients (34% vs 22% respectively, P = .04). The frequency of low voltage in the pretransplant cohort (47%) was twice that of the clinic cohort (24%, P < .001). After 1 year of follow-up in the clinic cohort, low ECG voltage was associated with a higher rate of death (14% vs 5%, P = .008) and the composite end point of death or HF hospitalization (35% vs 20%, P = .004). These associations persisted in multivariable analyses adjusting for important confounders. CONCLUSIONS: Low ECG voltage is a marker of the severity of HF and is a risk factor for adverse outcomes in patients with systolic HF at 1 year.

Treatment of the African-American patient with congestive heart failure.

African Americans have a higher burden of cardiovascular disease than white Americans, including a higher prevalence of heart failure. In addition, heart failure in African Americans conforms to a more malignant natural history. Hypertension is most often cited as the sole etiology of heart failure in African Americans. Most of the major trials of pharmacotherapy for the management of chronic heart failure have failed to include significant numbers of African-American patients. Based on the available evidence, there is no reason to withhold standard evidence-based medical therapy for heart failure. Even though there is much controversy as to the efficacy of angiotensin-converting enzyme (ACE) inhibitors and beta blockers in African Americans, in the absence of definitive data they should be used. Recently, the combination of isosorbide dinitrate and hydralazine has been demonstrated to improve survival in African Americans with New York Heart Association class III and IV heart failure, and represents an adjunctive treatment option when added to standard medical therapy consisting of ACE inhibitors, beta blockers, digoxin, diuretics, and aldosterone antagonists. Emerging evidence suggests that this therapy may be targeting a novel mechanism of heart failure progression (ie, nitric oxide bioavailability) found in African Americans.

Novel therapies for heart failure: vasopressin and selective aldosterone antagonists.

Despite favorable improvements in mortality, heart failure (HF) remains a problematic illness due to the ever-present burden of hospitalization. Clearly, novel treatment strategies are needed. This review focuses on two newer pharmacologic targets: arginine vasopressin and aldosterone. Arginine vasopressin receptor antagonists will most likely serve as an adjunct to or replacement of standard diuretic therapy in selected patients. The safety and efficacy of chronic therapy with oral arginine vasopressin receptor antagonists in large groups of congestive HF patients is currently under investigation. Aldosterone antagonism is emerging as a treatment of severe congestive HF. Recent large-scale clinical trials using aldosterone antagonists have proven that those with HF or left ventricular dysfunction postmyocardial infarction derive a survival benefit from aldosterone antagonism. Whether aldosterone antagonism should be prescribed in all patients with HF is unclear; however, in carefully selected and managed patients, aldosterone antagonism is helpful.

beta-Blocker therapy for congestive heart failure: clinical considerations.

Excessive activation of the sympathetic nervous system and local release of norepinephrine are detrimental to the failing myocardium. Blockade of the beta-adrenergic receptor system is now a potent strategy. Earlier concerns that beta-blockade would thwart compensatory mechanisms that preserve myocardial function are no longer valid in the compensated state. Over the past 2 decades, a large body of evidence has accrued indicating marked benefits in symptoms and survival as well as favorable changes in myocardial architecture with beta-blocker therapy in patients who have compensated heart failure with impaired systolic function. This article outlines the rationale for beta-blocker therapy, examines both the early and the large-scale clinical work with beta-blocker therapy for congestive heart failure, highlights additional novel aspects of beta-blocker therapy for heart failure, and outlines expert recommendations about the use of beta-blockers in patients with systolic dysfunction.