Elevated Lp(a): Guidance for Identifying and Managing Patients.

Lipoprotein(a) (Lp(a)) is a unique low-density lipoprotein-like lipoprotein that is considered an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis. The Lp(a) molecule also contains apolipoprotein A and apolipoprotein B, which collectively promote atherosclerosis, thrombosis, and inflammation. Lp(a) is highly genetic and minimally responsive to nonpharmacological measures. Lp(a) serum levels ≥125 nmol/L are associated with increased ASCVD risk, but this threshold has not been accepted universally. Elevated Lp(a) is the most common genetic dyslipidemia affecting approximately 20% of the general population. Certain currently available lipid-lowering drugs, including the proprotein convertase subtilisin/kexin type 9 therapies, produce moderate reductions in Lp(a); however, none are indicated for the treatment of elevated Lp(a). There are currently four investigational RNA-based therapeutic agents that reduce Lp(a) by 70% to 100%. Two of these agents are being evaluated for ASCVD risk reduction in adequately powered outcomes trials, with results expected in 2 to 3 years. Until such therapies become available and demonstrate favorable clinical outcomes, strategies for elevated Lp(a) primarily involve early and intensive ASCVD risk factor management.

Diet and exercise interventions following coronary artery bypass graft surgery: a review and call to action.

Coronary artery bypass graft (CABG) surgery has been used for the treatment of coronary artery disease (CAD) for approximately 50 years, and has been performed on millions of people globally. However, little is known about the impact of diet and exercise on long-term outcomes of patients who have undergone CABG surgery. Although clinical practice guidelines on the management of this patient population have been available for approximately 2 decades, evidence regarding secondary prevention behavioral interventions, lifestyle modifications and self-management to slow the progressive decline of CAD, reduce cardiac hospitalizations, and prevent reoperation remains virtually absent from the literature. Diet and exercise are modifiable factors that affect secondary CAD risk. This article reviews the relevant current literature on long-term diet and exercise outcomes in patients who underwent CABG. The limited available literature shows the positive impacts of exercise on psychosocial well-being and physical fitness. Current evidence indicates diet and exercise interventions are effective in the short-term, but effects fade over time. Potential age and sex differences were found across the reviewed studies; however, further research is needed with more rigorous designs to replicate and confirm findings, and to define optimal management regimens and cost-effective prevention strategies.

Electrocardiographic changes with the onset of diabetes and the impact of aerobic exercise training in the Zucker Diabetic Fatty (ZDF) rat.

BACKGROUND: Early markers of diabetic autonomic neuropathy (DAN) in an electrocardiogram (ECG) include elevated R wave amplitudes, widening of QTc intervals and decreased heart rate variability (HRV). The severity of DAN has a direct relationship with mortality risk. Aerobic exercise training is a common recommendation for the delay and possible reversal of cardiac dysfunction. Limited research exists on ECG measures for the evaluation of aerobic exercise training in Zucker Diabetic Fatty (ZDF) rat, a model of type 2 diabetes. The objective of this study was to assess whether aerobic exercise training may attenuate diabetes induced ECG changes. METHODS: Male ZDF (obese fa/fa) and control Zucker (lean fa/+) rats were assigned to 4 groups: sedentary control (SC), sedentary diabetic (SD), exercised control (EC) and exercised diabetic (ED). The exercised groups began 7 weeks of treadmill training after the development of diabetes in the ED group. Baseline (prior to the training) and termination measurements included body weight, heart weight, blood glucose and glycated hemoglobin levels and ECG parameters. One way repeated measures ANOVA (group) analyzed within and between subject differences and interactions. Pearson coefficients and descriptive statistics described variable relationships and animal characteristics. RESULTS: Diabetes caused crucial changes in R wave amplitudes (p < 0.001), heart rate variability (p < 0.01), QT intervals (p < 0.001) and QTc intervals (p < 0.001). R wave amplitude augmentation in SD rats from baseline to termination was ameliorated by exercise, resulting in R wave amplitude changes in ED animals similar to control rats. Aerobic exercise training neither attenuated QT or QTc interval prolongation nor restored decreases in HRV in diabetic rats. CONCLUSION: This study revealed alterations in R wave amplitudes, HRV, QT and QTc intervals in ZDF rats. Of these changes, aerobic exercise training was able to correct R wave amplitude changes. In addition, exercise has beneficial effect in this diabetic rat model in regards to ECG correlates of left ventricular mass.

Impact of bisphosphonates on the risk of atrial fibrillation.

Osteoporosis is a major public health problem resulting in significant morbidity, mortality, and utilization of healthcare resources. Bisphosphonates are the most widely prescribed drugs for increasing bone mass and preventing osteoporosis-related fractures. Although these drugs have proven efficacy and are generally considered safe, a clinical trial of once-yearly zoledronic acid reported an unexpected increase in the risk of cardiac arrhythmias, primarily due to serious atrial fibrillation (AF). Subsequently, a post hoc analysis of another clinical trial reported a nonsignificant trend toward an increased risk of serious AF. Based on these concerns, the US FDA issued a cautionary advisory and is conducting an ongoing safety review. A major limitation of the clinical trials was the fact that none were designed or powered to evaluate arrhythmia endpoints. In search of more definitive answers, several observational studies using both population-based cohort and case-control designs have attempted to verify this association. However, only two studies, one cohort and one case-control study, have found a positive association, while six additional studies have reported negative findings. While most of the observational studies attempted to control for confounders, the chosen variables have varied considerably, and other key potential confounders such as smoking were not controlled for in any of the studies. Because the occurrence of AF events in the studies was relatively low, four meta-analyses have been conducted to increase sample size by using pooled data from multiple studies. Again, results have been inconsistent, with two of the analyses reporting a significant increase in serious AF and two finding no association. Additionally, no direct evidence has identified any underlying mechanism to explain an increased arrhythmia risk with bisphosphonate therapy. However, several possible mechanisms have been proposed, including an activated inflammatory state, altered electrolytes impacting cardiac conduction, and long-term atrial structural changes. Due to the widespread use of bisphosphonates in a population for whom the baseline risk of AF also increases with advancing age, further prospective assessment of this possible association is clearly warranted. If an association does exist between bisphosphonates and an increased risk for AF, several additional questions will need to be answered including impact of baseline risk, the time course for increased risk, relationship to drug dose, and whether or not this represents a drug-class adverse effect. Until definitive evidence is available, clinicians will continue to have to make clinical judgments based on the available and often inconsistent evidence to date. To provide further perspective on this possible association, we performed a systematic search of the PubMed database from 1966 to 30 June 2010, drug regulatory websites, and drug manufacturer websites. In this review we summarize the findings from clinical trials, observational studies, and meta-analyses evaluating the risk of AF following bisphosphonate exposure, and discuss possible mechanisms that could explain an increased risk.

Approach to incidentally diagnosed isolated ventricular noncompaction of myocardium.

Isolated ventricular noncompaction (IVNC) is a congenital cardiomyopathy characterized by a distinctive ("spongy") morphological appearance of the left ventricular (LV) myocardium. It is rare but, with improved imaging modalities and awareness, it is being reported more frequently. Clinical manifestations may range from being asymptomatic to heart failure, arrhythmias, sudden cardiac death, and systemic thromboembolism. With the increasing reporting frequency, the implications of incidentally diagnosed noncompaction need to be addressed. We came across two cases at our medical center which raised important practical questions.

Potential Interaction between clopidogrel and proton pump inhibitors.

Clopidogrel is widely used in patients with acute coronary syndromes and following percutaneous coronary intervention with stent implantation. The antiplatelet action of clopidogrel is felt to be of critical importance for the reduction of abrupt thrombotic occlusion of stents, particularly with drug-eluting devices. When clopidogrel is used alone or in combination with aspirin (acetylsalicylic acid), the benefits of antiplatelet therapy must be weighed against the potential for serious bleeding, particularly gastrointestinal (GI) bleeds. To minimize the risk of GI injury, proton pump inhibitors (PPIs) are considered the drugs of choice. However, a growing body of evidence suggests that PPIs may adversely interact with clopidogrel, diminishing the antiplatelet effect. Although the current evidence remains controversial, the potential for increased risk of thrombotic complications warrants cautious use of this drug combination until further research can determine the extent of this interaction and whether it is a drug-class effect.

Understanding D-Ribose and Mitochondrial Function.

Mitochondria are important organelles referred to as cellular powerhouses for their unique properties of cellular energy production. With many pathologic conditions and aging, mitochondrial function declines, and there is a reduction in the production of adenosine triphosphate. The energy carrying molecule generated by cellular respiration and by pentose phosphate pathway, an alternative pathway of glucose metabolism. D-ribose is a naturally occurring monosaccharide found in the cells and particularly in the mitochondria is essential in energy production. Without sufficient energy, cells cannot maintain integrity and function. Supplemental D-ribose has been shown to improve cellular processes when there is mitochondrial dysfunction. When individuals take supplemental D-ribose, it can bypass part of the pentose pathway to produce D-ribose-5-phosphate for the production of energy. In this article, we review how energy is produced by cellular respiration, the pentose pathway, and the use of supplemental D-ribose.

Improving death certificate completion: a trial of two training interventions.

The death certificate is an important medical document that impacts mortality statistics and health care policy. Resident physician accuracy in completing death certificates is poor. We assessed the impact of two educational interventions on the quality of death certificate completion by resident physicians. Two-hundred and nineteen internal medicine residents were asked to complete a cause of death statement using a sample case of in-hospital death. Participants were randomized into one of two educational interventions: either an interactive workshop (group I) or provided with printed instruction material (group II). A total of 200 residents completed the study, with 100 in each group. At baseline, competency in death certificate completion was poor. Only 19% of residents achieved an optimal test score. Sixty percent erroneously identified a cardiac cause of death. The death certificate score improved significantly in both group I (14+/-6 vs 24+/-5, p<0.001) and group II (14+/-5 vs 19+/-5, p<0.001) postintervention from baseline. Group I had a higher degree of improvement than group II (24+/-5 vs 19+/-5, p<0.001). Resident physicians' skills in death certificate completion can be improved with an educational intervention. An interactive workshop is a more effective intervention than a printed handout.

A dilated inferior vena cava is a marker of poor survival.

BACKGROUND: The inferior vena cava (IVC) morphology is often used to estimate right atrial pressure; however, the association of IVC morphology and outcome is poorly described. METHODS: We evaluated 4383 consecutive outpatients (98% men) undergoing echocardiography at 1 of 3 Veterans Affairs laboratories. RESULTS: Of the 3729 with adequate images, 3295 (88%) had a normal IVC (< 2 cm), 358 (10%) had a dilated IVC that collapsed at least 50% with inspiration, and 76 (2%) had dilated IVC that did not collapse. Compared with patients with a normal IVC, those with a dilated IVC were older (66 +/- 13 vs 69 +/- 12 years if dilated with collapse and 70 +/- 12 years if dilated without collapse, P = .0005) and were more likely to have a history of heart failure (11% vs 18% if dilated with collapse and 38% if dilated without collapse, P < .0001). The 90-day and 1-year survival rates were 99% and 95% for those with a normal IVC, 98% and 91% for those with a dilated IVC with collapse, and 89% and 67% for those with a dilated IVC without collapse (P < .0001). After adjustment for clinical and echocardiographic characteristics including left and right ventricular function and pulmonary artery pressure, a dilated IVC without collapse remained associated with increased mortality: hazard ratio 1.43 (1.29-1.57 compared with a normal IVC, P < .0001). CONCLUSION: A dilated IVC without collapse with inspiration is associated with worse survival in men independent of a history of heart failure, other comorbidities, ventricular function, and pulmonary artery pressure.

Hemolytic anemia produced by regurgitation through transposed chordae tendineae.

Hemolytic anemia after mitral repair and annuloplasty ring placement is very uncommon, and rarely described. The case is presented of a 53-year-old woman who developed severe mitral regurgitation and transfusion-dependent hemolytic anemia following mitral valve repair with a Carpentier-Edwards annuloplasty ring, which included transposition of chordae tendineae from the posterior leaflet to the anterior leaflet. Transesophageal echocardiography suggested that the transposed chordae tethered the anterior leaflet, causing malcoaptation of the leaflets. This resulted in central regurgitation divided by the chordae tendineae, producing two turbulent flow jets causing hemolysis. At reoperation, these chordae were removed and two longer Gortex neochordae to the anterior leaflet were placed with subsequent resolution of the anemia. To the authors' knowledge, this is the first case of hemolytic anemia caused by transposed mitral valve chordae tendineae from the posterior to the anterior leaflet.

Caregiver coaching program effect: Reducing heart failure patient rehospitalizations and improving caregiver outcomes among African Americans.

OBJECTIVES: (1) Test whether FamHFcare intervention could reduce patients' heart failure (HF)-related rehospitalizations and improve family caregiver outcomes; (2) calculate effect size on caregiver outcomes; and (3) evaluate the FamHFcare. BACKGROUND: Few interventions target family caregivers for HF home care. METHODS: This study was a mixed method design with stratification and random assignment of 20 African American HF patient/caregiver dyads. Descriptive, univariate parametric/non-parametric, and post-hoc analyses were used. RESULTS: At 6 months, compared to standard care, the intervention group had significantly fewer HF rehospitalizations (M-W z = -1.8, p = 0.03), while caregiver confidence (M-W z = 2.8, p = 0.003) and social support scores (M-W z = 2.4, p = 0.01) were significantly higher, and caregiver depression (M-W z = -2.4, p = 0.01) were significantly lower. Caregivers rated the FamHFcare as helpful (M = 46.8 ± 4.1). CONCLUSIONS: The FamHFcare intervention was associated with fewer HF patient rehospitalizations and improved caregiver outcomes.

Disparities in lipid control and statin drug use among diabetics with noncoronary atherosclerotic vascular disease vs those with coronary artery disease.

BACKGROUND: Diabetes mellitus (DM), coronary artery disease (CAD), and noncoronary atherosclerotic vascular diseases (NCVDs) have similar risks of cardiovascular events and similar recommendations for lipid control. There are limited data regarding lipid control in diabetic patients with NCVD in current clinical practice. OBJECTIVE: To assess current day practice of lipid control in patients with DM with NCVD vs those with CAD. METHODS: We retrospectively identified 3336 patients with DM and known atherosclerotic vascular disease between January 2009 and March 2012. We compared demographic variables, lipid levels, and statin use in diabetics with CAD alone vs diabetics without CAD but with one or more NCVD. RESULTS: There were 234 patients in DM with NCVD group and 3102 patients in DM with CAD group. The DM with NCVD group had a higher mean total cholesterol (152 ± 40 vs 146 ± 42 mg/dL; P = .019) and mean low-density lipoprotein (LDL; 86 ± 35 vs 80 ± 34 mg/dL; P = .04) with only 70% of patients achieving LDL of <100 mg/dL (compared with 80% in the DM with CAD group; P < .001). Statin use was 100% in CAD vs 75% in NCVD group (P < .001). In addition to limited use of more potent statins in the NCVD group, there was also a significantly lower dose of statins used overall. CONCLUSION: Our study demonstrates lower use and less aggressive application of statins among diabetics with NCVD compared with diabetics with CAD, resulting in higher mean LDL and total cholesterol in the NCVD group.

Death certificate completion: how well are physicians trained and are cardiovascular causes overstated?

PURPOSE: To determine the ability of residents in completing death certificates correctly. METHODS: A total of 4800 residents were asked to complete a survey and cause-of-death statement using a sample case of in-hospital death due to urosepsis, of whom 590 residents (12%) responded. A scoring scale designed based on instructions from the National Association of Medical Examiners and the American College of Pathologists was used to measure responses quantitatively. RESULTS: Overall performance was poor, with only 23% (n = 137) of responses in the optimal scoring range. The average score was influenced significantly by level of residency training, as well as previous experience, prior formal training, and awareness of the guidelines regarding death certificate completion. Optimal scores correlated with level of residency training and prior formal training in death certificate completion, suggesting the benefits of experience and instruction. Forty-five percent (n = 267) of respondents incorrectly identified a cardiovascular event as the primary cause of death. CONCLUSION: The residents in this study demonstrated suboptimal performance in death certificate completion. Cardiovascular events were often incorrectly identified as the primary cause of death. Formal training can improve performance and should be emphasized in medical schools and residencies.

Differential benefits and outcomes of tirofiban vs abciximab for acute coronary syndromes in current clinical practice.

Little comparative data exist for glycoprotein IIb/IIIa inhibitors in acute coronary syndromes (ACS). Two hundred twenty-eight patients were studied: 114 received tirofiban (TI) and 114 received abciximab (AB) for either unstable angina (UA) or myocardial infarction (MI). All patients received aspirin, heparin, and ticlopidine or clopidogrel. Baseline characteristics were similar between the 2 groups for admitting diagnosis (UA vs MI), age, gender, ejection fraction, diabetes mellitus, prior coronary artery disease, prior myocardial infarction (MI), prior bypass surgery, hypertension, congestive heart failure, hyperlipidemia, MI type (Q vs non-Q), or location. Drug administration time (mean) was 13 hours (AB) and 24 hours (TI). All AB was administered in the catheterization laboratory as compared to TI (34% in laboratory and 66% before laboratory). More AB patients received angioplasty or stent (92% vs 80%, p = 0.008) while more TI patients had CABG (10% vs 3%, p = 0.027). In-hospital complications including death, MI, urgent revascularization, cerebrovascular accidents or transient ischemic attacks, and access site bleeding were similar (p = NS). Multivariate predictors of events (odds ratios) were prior coronary artery bypass graft (2.3), diabetes (1.7), and prior percutaneous transluminal coronary angioplasty (1.7), but not the agent used. Over a mean follow-up of 13 months, the individual endpoints of death, MI, revascularization, or hospitalization were similar for both groups. The AB patients had improved freedom from revascularization (100% vs 81%, p = 0.015) in an emergent setting and TI patients had improved freedom from revascularization (93% vs 77%, p = 0.038) with elective procedures. Tirofiban and abciximab appear effective and safe when used for ACS when recommended dosing and precautions are followed. Major adverse outcomes are rare and bleeding complications uncommon.

Practical strategies for cardiac disease prevention. Basic steps to ensure better heart health.

Primary care physicians are deluged with medical information from many sources: medical literature, public media and the Internet, the pharmaceutical and medical device industries, and patients themselves. How can a physician best deal with the volume of data provided by scientific research, medical education, drug promotion, popular opinion, government regulation, and payer constraints?