Late-onset Fabry disease: the cardiac sequela.

We describe a patient with Fabry disease (FD) who initially presented with atrial fibrillation without left ventricular hypertrophy (LVH) 14 years before being correctly diagnosed with FD. In the interim, he survived a myocardial infarction complicated by ventricular fibrillation, and his severe LVH was misdiagnosed as sarcomeric hypertrophic cardiomyopathy. In the following 4 years, he developed proteinuric kidney disease, neuropathy, sensorineural hearing loss and gastrointestinal symptoms. The patient was eventually readmitted for an overt heart failure (HF) exacerbation and was seen by an HF cardiologist. The constellation of systemic findings led to further diagnostic testing, including an endomyocardial biopsy, tests to determine alpha-galactosidase A enzyme activity and α-galactosidase A gene (GLA) analysis. The results of the patient's tests were consistent with FD and he was started on enzyme replacement therapy. To our knowledge, this is the first detailed description of a late-onset phenotype of FD with c.146 G>C GLA variant. In addition, this case serves as a potent reminder to pay meticulous attention to 'red flags' accompanying LVH.

Attainment of Guideline-Directed Medical Treatment in Stable Ischemic Heart Disease Patients With and Without Chronic Kidney Disease.

BACKGROUND: Stable ischemic heart disease (SIHD) is prevalent in patients with chronic kidney disease (CKD); however, whether guideline-directed medical therapy (GDMT) is adequately implemented in patients with SIHD and CKD is unknown. HYPOTHESIS: Use of GDMT and achievement of treatment targets would be higher in SIHD patients without CKD than in patients with CKD. METHODS: This was a retrospective study of 563 consecutive patients with SIHD (mean age 67.8 years, 84% Caucasians, 40% females). CKD was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73m2 using the four-variable MDRD Study equation. We examined the likelihood of achieving GDMT targets (prescription of high-intensity statins, antiplatelet agents, renin-angiotensin-aldosterone system inhibitors (RAASi), and low-density lipoprotein cholesterol levels < 70 mg/dL, blood pressure < 140/90 mmHg, and hemoglobin A1C < 7% if diabetes) in patients with (n = 166) and without CKD (n = 397). RESULTS: Compared with the non-CKD group, CKD patients were significantly older (72 vs 66 years; p < 0.001), more commonly female (49 vs 36%; p = 0.002), had a higher prevalence of diabetes (46 vs 34%; p = 0.004), and left ventricular systolic ejection fraction (LVEF) < 40% (23 vs. 10%, p < 0.001). All GDMT goals were achieved in 26% and 24% of patients with and without CKD, respectively (p = 0.712). There were no between-group differences in achieving individual GDMT goals with the exception of RAASi (CKD vs non-CKD: adjusted risk ratio 0.73, 95% CI 0.62-0.87; p < 0.001). CONCLUSIONS: Attainment of GDMT goals in SIHD patients with CKD was similar to patients without CKD, with the exception of lower rates of RAASi use in the CKD group.

Subcutaneous implantable cardioverter defibrillator for dialysis patients: a strategy to reduce central vein stenoses and infections.

Central venous stenosis is a common complication of the transvenous leads associated with an implantable cardioverter defibrillator (ICD). Although epicardial leads have been reported to bypass this complication, their placement is much more invasive than the subcutaneous ICDs (SICDs) and requires the services of a cardiothoracic surgeon. Recent data have demonstrated successful defibrillation using an SICD. In this report, we present 4 long-term hemodialysis patients treated successfully with an SICD. 3 patients received the device for primary prevention of sudden cardiac death (cardiomyopathy with low ejection fraction). The patient in the fourth case had a prolonged QT interval and received the device for secondary prevention. 3 patients had an arteriovenous fistula, whereas 1 patient was dialyzing with a tunneled dialysis catheter. Insertion of an SICD is a minimally invasive procedure. By virtue of leaving the venous system untouched, this approach might offer the advantage of reduced risk of central venous stenosis and infection over an endocardial ICD with transvenous leads. SICD is not experimental; it has been approved by the US Food and Drug Administration and is currently being used in the United States and Europe.

The heart failure clinic: a consensus statement of the Heart Failure Society of America.

BACKGROUND: Outpatient care accounts for a significant proportion of total heart failure (HF) expenditures. This observation, plus an expanding list of treatment options, has led to the development of the disease-specific HF clinic. METHODS AND RESULTS: The goals of the HF clinic are to reduce mortality and rehospitalization rates and improve quality of life for patients with HF through individualized patient care. A variety of staffing configurations can serve to meet these goals. Successful HF clinics require an ongoing commitment of resources, the application of established clinical practice guidelines, an appropriate infrastructure, and a culture of quality assessment. CONCLUSIONS: This consensus statement will identify the components of HF clinics, focusing on systems and procedures most likely to contribute to the consistent application of guidelines and, consequently, optimal patient care. The domains addressed are: disease management, functional assessment, quality of life assessment, medical therapy and drug evaluation, device evaluation, nutritional assessment, follow-up, advance planning, communication, provider education, and quality assessment.

Disparity in frequency of normal coronary artery in black and white patients undergoing cardiac catheterization.

BACKGROUND: Normal epicardial coronary arteries (NCA) based on angiography have been reported to occur more frequently in Blacks than in Whites, but these studies have suffered from the limitation of being retrospective, reporting on relatively small numbers of subjects, or lacking a systematic angiogram interpretation. METHODS AND RESULTS: Angiograms of 560 consecutive patients (226 Black and 334 White) enrolled in the Harlem-Bassett Study were reviewed. The presence of coronary artery disease risk factors was documented. A coronary artery was defined as normal if no segment contained a luminal diameter stenosis > 24%. Overall, NCA were found in 39.1% of patients (Blacks 42.9% and Whites 36.5%) and were present most frequently in White women (53.7%). Black men were two times more likely than White men to have NCA (odds ratio [OR] 2.09, P < .002). More Blacks than Whites with NCA were hypertensive (OR 3.30, P < .001) and cigarette smokers (OR 5.18, P < .001), whereas more Whites had hypercholesterolemia (OR .29, P < .001). CONCLUSION: Significant racial differences exist between the Black and White populations in regard to the presence of NCA. The traditional risk factors of age, diabetes, cigarette smoking, and hypercholesterolemia are present in both groups. However, a racial disparity exists in the frequency of some risk factors (hypertension, cigarette smoking, hypercholesterolemia) in patients with NCA.

Are there race/ethnicity differences in outpatient congestive heart failure management, hospital use, and mortality among an insured population?

OBJECTIVE: The objective of this study was to assess the quality of outpatient care received by patients with congestive heart failure (CHF) and whether differences in care and outcomes exist by race/ethnicity. BACKGROUND: Appropriate outpatient CHF management can improve patient well-being and reduce the need for costly inpatient care. Yet, little is known regarding outpatient CHF management or whether differences in this care exist by race/ethnicity. METHODS: Using automated data sources, we identified a cohort of insured patients seen in an outpatient setting for CHF between September 1992 and August 1993. Medical record abstraction was used to confirm diagnosis of CHF. Patients (N = 566) were followed until September 1998. Race/ethnicity differences in outpatient management and medical care utilization were assessed using generalized estimating equations. Differences in mortality and hospitalization for CHF, controlling for patient characteristics and outpatient management, were assessed using Cox and Andersen-Gill models, respectively. RESULTS: With the exception of beta blocker use and primary care visit frequency, few differences by race/ethnicity in patient characteristics and CHF management were found. However, older black patients had more hospital use both at baseline and during follow up. These differences persisted after adjusting for patient characteristics and clinical management. No race/ethnicity differences were found in mortality. CONCLUSIONS: In an insured population, older black patients with CHF have substantially more hospital use than older white patients. This increased use was not explained by differences in CHF outpatient management. Further research is needed to understand why race/ethnicity differences in hospital use are observed among older patients with CHF.

Lessons learned from the DIG trial.

The Digitalis Investigation Group (DIG) trial was the first large simple trial conducted by the National Heart, Lung, and Blood Institute in conjunction with the Department of Veterans Affairs. A large simple trial is a major undertaking. Simplification at the sites requires careful planning and discipline. Lessons learned from the DIG trial were: (1) keep a large simple trial very simple and keep all study procedures very simple; (2) ancillary studies are important and can complement a large simple trial but require careful advanced planning; (3) anticipate special needs when shipping study drugs internationally; (4) regional coordinating centers can be very useful; (5) recruit as many capable sites as possible; (6) provide research-inexperienced sites/investigators with extra help to obtain federalwide assurance statements from the Office for Human Research Protections and institutional review board approvals; (7) adequately reimburse sites for the work completed; (8) maintain investigator enthusiasm; (9) monitor the slow performers and sites with numerous personnel changes; (10) choose an endpoint that is easy to ascertain; (11) keep the trial simple for participants; and (12) plan early for closeout and for activities between the end of the trial and publication of results.

Angiotensin converting enzyme inhibitors and beta-blockers in African Americans with heart failure.

Previous analyses have implied diminished efficacy of angiotensin converting enzyme inhibitors (ACEI), and equivalent or enhanced efficacy of beta-blockers (BB), in African Americans (AA) with congestive heart failure (CHF), when compared to placebo. These results may have been influenced by lead-time bias, in that AA may not have been entered into the older ACEI trials until late in their CHF course. Our goal was to use a prospective cohort study of 29,686 CHF patients within a single health system to examine the impact on AA mortality of administering ACEI and BB within the first year of CHF diagnosis. Pharmacy claims from 1995-1998 were available for 3353 newly diagnosed CHF patients (39.2% AA; N=1317) within the health maintenance organization. Rates of ACEI and BB use were 46.4% and 54.0%; 43.4% and 28.9%; and 40.7% and 18.6%, for Whites, AA, and other races, respectively. The relative risk reductions (RRR) for ACEI were 68.7%, P<.0001; 52.1%, P<.0001; and -36.3%, P=.56, for Whites, AA, and other races, respectively. The RRR for BB were 59.0%, P<.0001; 34.6%, P=.009; and 74.3%, P=.17, for Whites, AA, and other races, respectively. Age- and gender-adjusted survival rates for AA were significantly enhanced in those taking ACEI, BB, or a combination of the two: P<.001, P=.001, and P=.003, respectively. Although we could not control for selection bias, these data suggest that AA benefit from both ACEI and BB when treatment is initiated within the first year of CHF diagnosis. Future, similar analyses other databases should control for the duration of illness to avoid lead-time bias in AA with CHF.

African Americans with LVH demonstrate depressed sensitivity of the coronary microcirculation to stimulated relaxation.

Excess coronary heart disease morbidity and mortality among African Americans remains an important yet unexplained public health problem. We hypothesized that adverse outcome is in part due to intrinsic or acquired abnormalities in coronary endothelial function and vasoreactivity. We compared dose-response curves relating changes in coronary blood flow and epicardial diameter to graded infusions of acetylcholine in 50 African American and 65 white subjects with hypertensive left ventricular hypertrophy (LVH) and normal coronary arteries. These groups were similar for age, body mass index, mean arterial pressure, and indexed left ventricular mass. The same protocol was conducted in 24 normotensive African American and 56 similar white subjects. We found significant depression in the coronary blood flow dose-response curve relation among African Americans when compared with white subjects with similar LVH (P<0.03). Racial differences were observed at all doses of acetylcholine but were less precisely estimated at the highest dose. The same testing among normotensive subjects revealed similar dose-response curves with no significant effect of race. Qualitatively similar results were found with respect to coronary diameter. Adenosine responses, a measure of endothelium-independent function, were similar after partitioning by LVH. Our study demonstrates that there are racial differences in sensitivity of coronary arteries to acetylcholine-stimulated relaxation among those with LVH. These results provide a mechanism whereby racial differences in coronary vasoreactivity might contribute to adverse coronary heart disease outcome among African Americans, a group in whom LVH is prevalent.

Opportunities for improvement in the diagnosis and treatment of heart failure.

BACKGROUND: Improved treatment of congestive heart failure (CHF) can slow disease progression, promote clinical stability, and prolong survival. HYPOTHESIS: Patterns in diagnostic test utilization and pharmacotherapy among patients with newly diagnosed heart failure may affect outcomes. METHODS: Claims data were analyzed from all diagnostic procedures and prescriptions from 1995 to 1998 in 3,353 patients with heart failure diagnosed within 1 year. Rates of diagnostic testing and categories of drugs prescribed were the main outcome measures. Demographic variables and type of provider were analyzed within a setting whose access to care was controlled. RESULTS: Rates of diagnostic testing with respect to basic, metabolic/endocrine, alternative diagnoses, underlying ischemia, and left ventricular function varied as a function of gender, age, race, and primary versus specialty care provider. Only 4.7% of patients underwent all diagnostics and treatments recommended in current guidelines. However, those patients (27.5%) who underwent an evaluation for ischemic heart disease and were prescribed vasodilators or beta blockers enjoyed the lowest crude mortality. CONCLUSIONS: There are multiple opportunities apparent to improve the initial diagnostic and therapeutic care of patients with heart failure. There appears to be an early survival benefit with respect to use of vasodilators and beta blockers within the first year of treatment.

Improving outcomes in diastolic heart failure. Techniques to evaluate underlying causes and target therapy.

Abnormal diastolic function is a common cause of clinical heart failure, particularly among elderly patients. Through early diagnosis and careful management of diastolic dysfunction, these patients can expect improved functional capacity and, in some cases, a favorable long-term outcome. In this article, Drs Torosoff and Philbin discuss how to confirm the diagnosis of diastolic heart failure through objective testing. Current approaches to the treatment of symptoms, including reduction of intravascular volume, heart rate control, and elimination of precipitating factors, are also presented.

The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine.

OBJECTIVES: The purpose of our study was to determine if the presence of African American ethnicity modulates improvement in coronary vascular endothelial function after supplementary L-arginine. BACKGROUND: Endothelial dysfunction is an early stage in the development of coronary atherosclerosis and has been implicated in the pathogenesis of hypertension and cardiomyopathy. Amelioration of endothelial dysfunction has been demonstrated in patients with established coronary atherosclerosis or with risk factors in response to infusion of L-arginine, the precursor of nitric oxide. Racial and gender patterns in L-arginine responsiveness have not, heretofore, been studied. METHODS: Invasive testing of coronary artery and microvascular reactivity in response to graded intracoronary infusions of acetylcholine (ACh) +/- L-arginine was carried out in 33 matched pairs of African American and white subjects with no angiographic coronary artery disease. Pairs were matched for age, gender, indexed left ventricular mass, body mass index and low-density lipoprotein cholesterol. RESULTS: In addition to the matching parameters, there were no significant differences in peak coronary blood flow (CBF) response to intracoronary adenosine or in the peak CBF response to ACh before L-arginine infusion. However, absolute percentile improvement in CBF response to ACh infusion after L-arginine, as compared with before, was significantly greater among African Americans as a group (45 +/- 10% vs. 4 +/- 6%, p = 0.0016) and after partitioning by gender. The mechanism of this increase was mediated through further reduction in coronary microvascular resistance. L-arginine infusion also resulted in greater epicardial dilator response after ACh among African Americans. CONCLUSIONS: We conclude that intracoronary infusion of L-arginine provides significantly greater augmentation of endothelium-dependent vascular relaxation in those of African American ethnicity when compared with matched white subjects drawn from a cohort electively referred for coronary angiography. Our findings suggest that there are target populations in which supplementary L-arginine may be of therapeutic benefit in the amelioration of microvascular endothelial dysfunction. In view of the excess prevalence of cardiomyopathy among African Americans, pharmacologic correction of microcirculatory endothelial dysfunction in this group is an important area of further investigation and may ultimately prove to be clinically indicated.

Hospital outcomes in major teaching, minor teaching, and nonteaching hospitals in New York state.

PURPOSE: The possible benefit that hospital teaching status may confer in the care of patients with cardiovascular disease is unknown. Our purpose was to determine the effect of hospital teaching status on in-hospital mortality, use of invasive procedures, length of stay, and charges in patients with myocardial infarction, heart failure, or stroke. SUBJECTS AND METHODS: We analyzed a New York State hospital administrative database containing information on 388 964 consecutive patients who had been admitted with heart failure (n = 173 799), myocardial infarction (n = 121 209), or stroke (n = 93 956) from 1993 to 1995. We classified the 248 participating acute care hospitals by teaching status (major, minor, nonteaching). The primary outcomes were standardized in-hospital mortality ratios, defined as the ratio of observed to predicted mortality. RESULTS: Standardized in-hospital mortality ratios were significantly lower in major teaching hospitals (0.976 for heart failure, 0.945 for myocardial infarction, 0.958 for stroke) than in nonteaching hospitals (1.01 for heart failure, 1.01 for myocardial infarction, 0.995 for stroke). Standardized in-hospital mortality ratios were significantly higher for patients with stroke (1.06) but not heart failure (1.0) or myocardial infarction (1.06) in minor teaching hospitals than in nonteaching hospitals. Compared with nonteaching hospitals, use of invasive cardiac procedures and adjusted hospital charges were significantly greater in major and minor teaching hospitals for all three conditions. The adjusted length of stay was also shorter for myocardial infarction in major teaching hospitals and longer for stroke in minor teaching hospitals. CONCLUSION: Major teaching hospital status was an important determinant of outcomes in patients hospitalized with myocardial infarction, heart failure, or stroke in New York State.

Confirmation of a heart failure epidemic: findings from the Resource Utilization Among Congestive Heart Failure (REACH) study.

OBJECTIVES: The purpose of this study was to create an automated surveillance tool for reporting the incidence, prevalence and processes of care for patients with heart failure. BACKGROUND: Previous epidemiologic studies suggest that the increasing prevalence of heart failure is a consequence of improved survival coupled with minimal changes in disease prevention. Developing new, efficient methods of assessing the incidence and prevalence of heart failure could allow continued surveillance of these rates during an era of rapidly changing treatments and health care delivery patterns. METHODS: Using administrative data sets, we created a definition of heart failure using diagnosis codes. After adjustment for patients leaving our health system or death, we derived the incidence, prevalence and mortality of the population with heart failure from 1989 to 1999. RESULTS: A total of 29,686 patients of all ages, 52.6% women and 47.4% men, met the definition of heart failure. Mean ages were 71.1 +/- 14.5 for women and 67.7 +/- 14.4 for men, p < 0.0001. Race proportions were 50.5% white, 44.6% African American and 4.9% other race. Incidence rates were higher in men and African Americans across all age groups. There was an annual increase in prevalence of 1/1,000 for women and 0.9/1,000 for men, p = 0.001 for both trends. CONCLUSIONS: Through the feasible and valid use of automated data, we have confirmed a chronic disease epidemic of heart failure manifested primarily by an increase in prevalence over the past decade. Our surveillance system mirrors the results of epidemiologic studies and may be a valid method for monitoring the impact of prevention and treatment programs.