Shadwan Alsafwah

Hypovitaminosis D in African Americans residing in Memphis, Tennessee with and without heart failure

Background:Factors contributing to heart failure (HF) in African Americans (AA) are under investigation. Reduced 25(OH)D confers increased cardiovascular risk, including HF. Methods:We monitored serum 25(OH)D, 1,25(OH)2D3, parathyroid hormone (PTH), and creatinine clearance in 102 AA residing in Memphis: 58 hospitalized with decompensated HF of ≥4 weeks in 34 (21 men; 53.3 ± 1.8 years) or of 1 to 2 weeks in 24 (17 men; 49.6 ± 2.4 years) and associated with a dilated cardiomyopathy and reduced ejection fraction (<35%); 19 outpatients with compensated HF (14 men; 52.6 ± 2.7 years) with comparable ejection fraction; 16 outpatients (9 men; 55.4 ± 2.9 years) with heart disease, but without HF; and 9 healthy volunteers (3 men; 35.8 ± 3.5 years). Results:Serum 25(OH)D ≤30 ng/mL was found in 96% and 90% with protracted or short-term decompensated HF, where it was of moderate to marked severity (<20 ng/mL) in 83% and 76%, respectively. In patients with either compensated or no HF, 25(OH)D <30 ng/mL was found in 95% and 100%, respectively, and in 30% of volunteers. Normal serum 1,25(OH)2D3 did not differ between patients. Serum PTH >65 pg/mL was found in all AA with decompensated HF of ≥4 weeks (132.4 ± 12.0 pg/mL) and 67% with 1 to 2 weeks duration (82.3 ± 7.9 pg/mL), but only 11% with compensated HF (45.8 ± 6.1 pg/mL), 12% without HF (29.6 ± 5.4 pg/mL), and none of the volunteers (31.1 ± 3.9 pg/mL). Creatinine clearance did not differ between patient groups. Conclusions:Hypovitaminosis D is prevalent amongst AA residing in Memphis, with or without HF. Elevations in serum PTH in keeping with secondary hyperparathyroidism are only found in AA with decompensated HF, where hypovitaminosis D and other factors are contributory.

Congestive Heart Failure is a Systemic Illness: A Role for Minerals and Micronutrients

Congestive heart failure (CHF) is a clinical syndrome that features a failing heart together with signs and symptoms arising from renal retention of salt and water, mediated by attendant neurohormonal activation, and which prominently includes the renin-angiotensin-aldosterone system. More than this cardiorenal perspective, CHF is accompanied by a systemic illness whose features include an altered redox state in diverse tissues and blood, an immunostimulatory state with proinflammatory cytokines and activated lymphocytes and monocytes, and a wasting of tissues that includes muscle and bone. Based on experimental studies of aldosteronism and clinical findings in patients with CHF, there is an emerging body of evidence that secondary hyperparathyroidism is a covariant of CHF. The aldosteronism of CHF predisposes patients to secondary hyperparathyroidism because of a chronic increase in Ca2+ and Mg2+ losses in urine and feces, with a fall in their serum ionized levels and consequent secretion of parathyroid hormone. Secondary hyperparathyroidism accounts for bone resorption and contributes to a fall in bone strength that can lead to nontraumatic fractures.The long-term use of a loop diuretic with its attendant urinary wasting of Ca2+ and Mg2+ further predisposes patients to secondary hyperparathyroidism and attendant bone loss. Aberrations in minerals and micronutrient homeostasis that includes Ca2+, Mg2+, vitamin D, zinc and selenium appear to be an integral component of pathophysiologic expressions of CHF that contributes to its systemic and progressive nature. This broader perspective of CHF, which focuses on the importance of secondary hyperparathyroidism and minerals and micronutrients, raises the prospect that dietary supplements could prove remedial in combination with the current standard of care.

Evidence for the existence of a distinct SO(4)(--)-OH(-) exchange mechanism in the human proximal colonic apical membrane vesicles and its possible role in chloride transport.

Recent studies have demonstrated that mutations in human downregulated in adenoma gene (DRA) result in congenital chloride diarrhea (CLD), and that DRA may be involved in chloride transport across the intestinal apical domains. DRA is highly homologous to sulfate transporters, but not to any member of the anion exchanger gene family (AEs). Our previous studies have characterized the existence of a distinct CI–-OH– (HCO3–) exchanger, with minimal affinity for sulfate in the human colonic apical membrane vesicles (AMV). However, the mechanism(s) of sulfate movement across the colonocyte plasma membranes in the human colon is not well understood. Current studies were undertaken to elucidate sulfate transport pathways in AMVs of human proximal colon. Purified AMV and rapid filtration 35SO–4 uptake techniques were used. Our results demonstrate the presence of a pH gradient-driven carrier-mediated SO–4-OH– exchange process in the human proximal colonic luminal membranes based on the following: a marked increase in the SO–4 uptake in the presence of an outwardly directed OH- gradient; a significant inhibition of SO–4 uptake by the membrane anion transport inhibitor, DIDS; demonstration of saturation kinetics (Km for SO–4 0.80 ± 0.17 mM and Vmax 649 ± 74 pmol/mg protein/10 sec); competitive inhibition of SO–4-OH– exchange by oxalate; SO–4 uptake was insensitive to alterations in the membrane potential; and inwardly directed Na+ gradient under non-pH gradient conditions did not stimulate SO–4 uptake. SO–4 uptake was significantly inhibited by increasing concentrations of chloride (1–10 mM) in the incubation media with a Ki, for CI– of 9.3 ± 1.4 mM. In contrast, OH–/HCO3– gradient-driven 36CI– uptake into these vesicles was unaffected by increasing concentrations of sulfate (10–50 mM). The above data indicate that two distinct transporters may be involved in SO–4 and CI– transport In the human intestinal apical membranes: an anion exchanger with high affinity for SO–4 and oxalate but low affinity for CI–, and a distinct CI–-OH– (HCO3–) exchanger with low affinity for SO–4.

A rare case of nonobstructive membrane of the left atrial appendage

The left atrial appendage (LAA) is a blind‐ending, complex structure distinct from the body of the left atrium and is sometimes regarded as a minor extension of the atrium. However, it should routinely be evaluated as part of a transesophageal echocardiographic examination. In this study we describe the presence of a nonobstructive membrane traversing the cavity of the LAA, found incidentally on transesophageal echocardiography.

Giant right atrial mass obliterating the right atrium

A73-year-old man with past medical history of mechanical aortic valve replacement, metastatic melanoma of unknown primaries with liver metastasis, presented with progressive shortness of breath and dyspnea on exertion. Transthoracic echocardiography (TTE) showed a large homogenous mass completely occupying the right atrial cavity and extending to and nearly obstructing the inflow area of the tricuspid valve. He was treated with chemotherapy.

Fatal spontaneous left main coronary artery thrombosis as a rare complication of noncardiac surgery

A 72-year-old man with a history of anterior wall myocardial infarction, who had stenting to his left anterior descending artery, developed an acute episode of dyspnea, hypoxemia and anginal chest pain three days after above-the-knee amputation for dry gangrene of the left leg. A physical examination revealed bilateral lung rales and a soft ejection systolic murmur at the left sternal border. Transient new lateral ST segment elevation associated with reciprocal inferior ST segment depression and prior anterior-septal infarct were evident on his electrocardiogram. Cardiac catheterization showed a filling defect in the middle segment of the left main coronary artery (Figure 1). During the procedure, the patient became more dyspneic and developed fatal cardiopulmonary arrest; he did not respond to resuscitative measures (1). Figure 1) Coronary angiogram showing a filling defect (arrow) in the middle segment of the left main coronary artery, representing a thrombus. Also noted was severe in-stent stenosis of the proximal left anterior descending artery

Paradoxical Hemodynamic Instability After Pericardial Window.

Paradoxical hemodynamic instability (PHI), also called postoperative low cardiac output syndrome (LCOS), is a rare but fatal complication after drainage of a pericardial effusion (PEf). This condition usually develops within hours postprocedure and appears unrelated to the method of drainage. The exact mechanism of this condition is not well understood. We present a case of an 84‐year‐old patient with no previous cardiac or cancer history who presented with acute shortness of breath (SOB). Computed tomography (CT) ruled out pulmonary embolism and echocardiography confirmed early tamponade. Following emergent subxiphoid pericardiectomy, the patient developed hemodynamic instability and shock and subsequent multiorgan failure. Repeat echocardiography revealed left ventricular (LV) hypercontractility and new right ventricular (RV) dilatation with akinesis. The patients condition continued to deteriorate in spite of maximal doses of pressors. The patient died after the familys request to discontinue further extraordinary measures.

A Mitochondriocentric Pathway to Cardiomyocyte Necrosis: An Upstream Molecular Mechanism in Myocardial Fibrosis

The pathophysiologic origins of heart failure can be attributed to a pathologic remodeling of myocardium, including necrotic loss of cardiomyocytes and consequent reparative fibrosis. Hypertensive heart disease with concentric left ventricular hypertrophy and fibrosis represents a major etiologic factor accounting for diastolic heart failure. Herein, we focus on molecular mechanisms to the precursor of fibrosis, namely, cardiomyocyte necrosis, whose pathogenic origin resides in a mitochondriocentric signal-transducer–effector pathway. Its major components include intracellular Ca2+ overloading of cytosolic and mitochondrial domains, the induction of oxidative stress by these organelles which overwhelms endogenous antioxidant defenses, and the increased opening potential of the mitochondrial permeability transition pore. Novel cardioprotective strategies aimed at preventing the progressive remodeling of the failing heart should target upstream molecular mechanisms that prevent cardiomyocyte necrosis rather than downstream events involving collagen turnover related to fibrosis.

Mediastinal hematoma causing compression of the right ventricular outflow tract – the role of transthoracic echocardiography in diagnosis

A 57-year-old man presented with acute coronary syndrome for which he was initially treated medically with a regimen that included acetylsalicylic acid, clopidogrel and heparin. Later, he was found to have two-vessel coronary artery disease requiring coronary artery bypass grafting. His postoperative period was complicated by hypotension and excessive bleeding, requiring multiple transfusions of blood products. His continued hemodynamic instability led to the suspicion of a mechanical complication. A transthoracic left parasternal short-axis view at the mitral valve level showed an anterior mediastinal hematoma compressing the right ventricular outflow tract (Figure 1). Figure 1) Transthoracic left parasternal short-axis view showing an anterior mediastinal hematoma (MH) compressing the right ventricular outflow tract. LV Left ventricle; RV Right ventricle The hematoma was also compressing the main pulmonary artery with its bifurcation, as well as the aorta, as shown by the transthoracic high right parasternal short-axis view (Figure 2). Figure 2) Transthoracic high right parasternal short-axis view showing the mediastinal hematoma (MH) compressing the aorta (Ao), as well as the main pulmonary artery with its bifurcation. LMPA Left main pulmonary artery The patient was taken back to the operating room, where the hematoma was evacuated. He did very well after that and left the hospital five days later (1).

Quadricuspid aortic valve infective endocarditis

Infective endocarditis complicating a quadricuspid aortic valve (QAV) is rare. Previous reports highlight the increased risk for complications, including progressive aortic regurgitation, decompensated heart failure, and valve perforation. Thus, cardiologists must be able to quickly identify QAVs to guide rapid evaluation and treatment. We report a case of infective endocarditis in a QAV identified on echocardiography and effectively managed with medical therapy alone without complications over an 8‐year follow‐up period.