Supplemental vitamin D and calcium in the management of African Americans with heart failure having hypovitaminosis D.

INTRODUCTION: A dyshomeostasis of macro- and micronutrients, including vitamin D and oxidative stress, are common pathophysiologic features in patients with congestive heart failure (CHF). In African Americans (AA) with CHF, reductions in plasma 25(OH)D are of moderate-to-marked severity (<20 ng/mL) and may be accompanied by ionized hypocalcemia with compensatory increases in serum parathyroid hormone (PTH). The management of hypovitaminosis D in AA with CHF has not been established. METHODS: Herein, a 14-week regimen: an initial 8 weeks of oral ergocalciferol (50,000 IU once weekly); followed by a 6-week maintenance phase of cholecalciferol (1400 IU daily); and a CaCO3 (1000 mg daily) supplement given throughout was designed and tested. Fourteen AA patients having a dilated (idiopathic) cardiomyopathy with reduced ejection fraction (EF, <35%) were enrolled: all completed the initial 8-week course; and 12 complied with the full 14 weeks. At baseline, 8 and/or 14 weeks, serum 25(OH)D and PTH; serum 8-isoprostane, a biomarker of lipid peroxidation, and echocardiographic EF were monitored. RESULTS: Reduced 25(OH)D at entry (14.4 ± 1.3 ng/mL) was improved (P < 0.05) in all patients at 8 weeks (30.7 ± 3.2 ng/mL) and sustained (P < 0.05) at 14 weeks (30.9 ± 2.8 ng/mL). Serum PTH, abnormally increased in 5 patients at baseline (104.8 ± 8.2 pg/mL), was reduced at 8 and 14 weeks (74.4 ± 18.3 and 73.8 ± 13.0 pg/mL, respectively). Plasma 8-isoprostane at entry (136.1 ± 8.8 pg/mL) was reduced at 14 weeks (117.8 ± 7.8 pg/mL; P < 0.05), whereas baseline EF (24.3 ± 1.7%) was improved (31.3 ± 4.3%; P < 0.05). CONCLUSIONS: Thus, the 14-week course of supplemental vitamin D and CaCO3 led to healthy 25(OH)D levels in AA with heart failure having vitamin D deficiency of moderate-to-marked severity. Albeit a small patient population, the findings suggest that this regimen may attenuate the accompanying secondary hyperparathyroidism and oxidative stress and improve ventricular function.

From aldosteronism to oxidative stress: the role of excessive intracellular calcium accumulation.

Inappropriately (relative to dietary Na(+)) elevated plasma aldosterone concentrations (PAC), or aldosteronism, have been incriminated in both the appearance of the cardiometabolic syndrome (CMS) and its progressive nature. The deleterious dual consequences of elevated PAC and dietary Na(+) have been linked to several components of the CMS, including salt-sensitive hypertension. Moreover, their adverse consequences are considered to be synergistic, culminating in a pro-oxidant phenotype with oxidative injury involving the heart and systemic tissues, including peripheral blood mononuclear cells (PBMC). Our experimental studies in rats receiving aldosterone/salt treatment have identified a common pathogenic event that links aldosteronism to the induction of oxidative stress. Herein, we review these findings and the important role of excessive intracellular Ca(2+) accumulation (EICA), or intracellular Ca(2+) overloading, which occurs in the heart and PBMC, leading to, respectively, cardiomyocyte necrosis with a replacement fibrosis and an immunostimulatory state with consequent coronary vasculopathy. The origin of EICA is based on elevations in plasma parathyroid hormone, which are integral to the genesis of secondary hyperparathyroidism that accompanies aldosteronism and occurs in response to plasma-ionized hypocalcemia and hypomagnesemia whose appearance is the consequence of marked urinary and fecal excretory losses of Ca(2+) and Mg(2+). In addition, we found intracellular Ca(2+) overloading to be intrinsically coupled to a dyshomeostasis of intracellular Zn(2+), which together regulate the redox state of cardiac myocytes and mitochondria via the induction of oxidative stress and generation of antioxidant defenses, respectively. To validate our hypothesis, a series of site-directed, sequential pharmacological and/or nutriceutical interventions targeted along cellular-molecular cascades were carried out to either block downstream events leading to the pro-oxidant phenotype or to enhance antioxidant defenses. In each case, the interventions were found to be cardioprotective. These cumulative salutary responses raise the prospect that pharmacological agents and nutriceuticals capable of influencing extra- and intracellular Ca(2+) and Zn(2+) equilibrium could prevent adverse cardiac remodeling and thereby enhance the management of aldosteronism.

Causes and consequences of systemic venous hypertension.

The causes of systemic venous hypertension (SVHT) include cardiac- and circulatory-related factors, whereas its consequences include the congestion of hepatic, splanchnic, and peripheral circulations, which contribute significantly to the clinical congestive heart failure syndrome. Based on a disequilibrium in hydrostatic and oncotic pressures, the increased filtration and formation of interstitial fluid at these sites with an accompanying increase in lymph flow mandates an increment in lymphatic drainage to protect against such congestion and the appearance of edema and ascites. However, lymph flow via the thoracic duct into systemic veins is opposed by elevations in central venous pressure. Various management strategies have the potential to prevent and/or correct SVHT. The case of a 54-year-old man with a dilated cardiomyopathy who presented with decompensated biventricular failure, expressed as anasarca and ascites, is used to illustrate the importance of SVHT.

Previous percutaneous coronary intervention may increase symptom recurrence and adverse cardiac events following surgical revascularization.

OBJECTIVE: The number of percutaneous coronary interventions (PCI) is increasing. There is limited outcome data on patients with a history of PCI and subsequently required surgical revascularization. METHODS: Overall 611 patients who survived 30 days after coronary artery bypass graft surgery (CABG) between 2001 and 2005 were evaluated. Mean follow-up was 29.4 +/- 11.3 months and 45% were female. The effect of preoperative PCI as a risk factor for symptom recurrence and adverse cardiovascular events and mortality was determined. RESULTS: Preoperative PCI was an independent risk factor for symptom recurrence (p<0.0001), combined adverse cardiac events (p<0.0001) and slightly increased overall mortality (p<0.04). Comparison of patients with and without a prior PCI showed that former had significantly worse outcomes compared to the latter. Patients with history of at least one restenosis following a PCI developed significantly more adverse end points (p<0.0001). CONCLUSION: In this study, patients with previous PCI were more likely to develop symptom recurrence and adverse cardiovascular events following CABG. This difference was more pronounced in patients who had at least one recurrent stenosis after a PCI.

Postoperative clopidogrel improves mid-term outcome after off-pump coronary artery bypass graft surgery: a prospective study.

OBJECTIVE: Clopidogrel decreases recurrent ischemic events and improves intracoronary stent patency. There are scarce data on the effect of short-term and long-term clopidogrel on symptom recurrence and adverse cardiac events following off-pump coronary artery bypass graft surgery (OPCAB). METHODS: Postoperative antiplatelet medication use was prospectively evaluated in 591 OPCAB patients. Clopidogrel was administered for 30 days in 186 patients and 139 received long-term clopidogrel (mean 33.6+/-12.0 months) in addition to aspirin. Follow-up was 37.7+/-13.4 months. Symptom recurrence (angina and congestive heart failure), adverse cardiac events (myocardial infarction, coronary reintervention, and sudden cardiac death), and overall mortality were prospectively recorded. Multivariate Cox regression analysis was used to evaluate predictors of end points. RESULTS: There was no difference with respect to preoperative risk factors between patient groups. In the multivariate analysis, postoperative clopidogrel independently decreased symptom recurrence (p<0.0001, OR 0.3 [0.15-0.99]; 95% CI) and adverse cardiac events (p<0.0001, OR 0.2 [0.10-0.45]; 95% CI). Clopidogrel receivers had significantly lower angina recurrence, myocardial infarction, coronary reintervention, and sudden cardiac death during follow-up. There was no difference in the incidence of end points between short-term (30 days) and long-term receivers of the drug. There were 17 bleeding complications (4 major and 13 minor) in 15 patients during the follow-up period. Of the 15 patients, 6 were on clopidogrel in addition to aspirin (1.8%) while the remaining 9 were on aspirin (3.3%) only at the time of bleeding (p=0.8). CONCLUSIONS: Clopidogrel therapy was independently associated with decreased symptom recurrence and adverse cardiac events following OPCAB. Extending clopidogrel use beyond 30 days did not have a significant effect on defined end points.

Predictors of mid-term symptom recurrence, adverse cardiac events and mortality in 591 unselected off-pump coronary artery bypass graft patients.

BACKGROUND: Off-pump coronary artery bypass (OPCAB) grafting is gaining popularity; however, decreased mid-term graft patency and increased coronary reintervention rates are reported. STUDY DESIGN: Five hundred and ninety-one consecutive unselected patients underwent OPCAB grafting from February 2000 to April 2004 (mean follow-up 38.54 +/- 0.54 months). One hundred and thirteen patients had < or =2 grafts, and four hundred and seventy-eight had > or =3 grafts. At least one radial artery graft was present in 398 patients, 328 received postoperative Clopidogrel, and 391 received postoperative statins. History of at least one percutaneous coronary intervention (PCI) was present in 192 patients. RESULTS: Twenty-nine patients developed recurrent angina, nine had myocardial infraction, and twenty underwent coronary reintervention. Five patients died of sudden cardiac death. Overall mortality was 4.9% during follow-up (29 patients). Postoperative Clopidogrel and statins as well as intraoperative shunt use significantly decreased symptom recurrence and adverse cardiac events. Diabetes, chronic obstructive pulmonary disease, prior history of PCI, and utilization of radial artery grafts were positive predictors of symptom recurrence and adverse cardiac events. Utilization of radial artery grafts, history of PCI as well as low preoperative ejection fraction increased mortality. Number of bypass grafts, type of conduit, grafted territory, hyperlipidemia, or prior coronary artery bypass graft surgery (CABG) did not influence symptom recurrence, adverse cardiac events or mortality. CONCLUSIONS: OPCAB grafting can be performed with low symptom recurrence, adverse cardiac events, and mortality rates. Modification of intra- and postoperative management strategies may improve outcomes.

Heparin-induced thrombocytopenia in the cardiovascular patient: diagnostic and treatment guidelines.

Heparin-induced thrombocytopenia/thrombosis is an immunologic reaction to unfractionated heparin characterized by thrombocytopenia, platelet activation and thrombosis. A high index of suspicion is required for timely diagnosis and treatment. Treatment is complex and outcome maybe less then satisfactory.