Valvular heart disease: a primer for the clinical pharmacist.

Valvular heart disease is a commonly encountered clinical condition that is not taught in most undergraduate and graduate pharmacy programs, leaving the practicing pharmacist without basic knowledge to expand on and subsequently apply to direct patient care. Unlike other areas of cardiology in which thousands of patients are recruited in many well-designed randomized clinical trials, data assessing treatments for valvular heart disease are limited and often consist of retrospective case series or observations. Our goal is to provide a basic overview of chronic valvular heart disease, with emphasis on describing the common conditions requiring surgery and the available options, as well as common pharmacologic therapies used in this patient population. Anomalies in valves can be broadly classified as stenosis and regurgitation. Depending on the valve and the type of anomaly, the impact on the cardiovascular system will vary. Understanding the hemodynamic consequences of aortic stenosis, aortic regurgitation, mitral stenosis, and mitral regurgitation is imperative to effectively counsel patients surrounding disease progression and self-monitoring, use of vasodilators, and prophylaxis for endocarditis and rheumatic fever. Further, patient characteristics factored into the choice of implanting either a bioprosthetic (tissue) or prosthetic (metal) valve encompass patient choice, life expectancy, and willingness or ability to accept lifelong anticoagulation therapy. The evolution of metal valves has resulted in newer generations under clinical study that have more laminar flow (minimizing interaction with blood products) and improved pyrolytic carbon (minimizing infection and interaction with blood products). Although antithrombotic therapy with warfarin is now mandatory in North America for all patients receiving metal valves, research is ongoing to assess the need with the most recent generation of valves.

Interpretation of exercise stress test recordings: concordance between nurse practitioner and cardiologist.

AIM: Cardiology nurse practitioners (NPs) conduct exercise stress tests (ESTs) for diagnosis of cardiac disease. The diagnostic concordance of NPs to cardiologists has not been assessed. The hypothesis was that an NP is as reliable as a cardiologist in determining ST-segment depression, detecting arrhythmias, and making a diagnostic assessment. METHODS: An NP and two cardiologists (C1 and C2) were provided with 100 consecutive, anonymized ESTs, consisting of three 10-second, 12-lead tracings obtained at baseline, peak-exercise, and recovery. Interpretation was based on baseline rhythm, baseline and maximal exercise ST levels, arrhythmias, and global diagnosis (positive, negative, or inconclusive for ischemia). Raters used uniform criteria to interpret ESTs and were blinded to prior EST interpretation and computerized ST-segment analysis. RESULTS: There was similar concordance between the NP and cardiologists as between the cardiologists, measured by Kappa coefficients (rhythm: NP vs. C1 = .92, NP vs. C2 = .84, C1 vs. C2 = .84; arrhythmias: NP vs. C1 = .77, NP vs. C2 = .73, C1 vs. C2 = .75; EST diagnosis: NP vs. C1 = .75, NP vs. C2 = .73, C1 vs. C2 = .75). Pearson correlations demonstrated concordance for baseline ST levels (NP vs. C1 = .86, NP vs. C2 = .86, C1 vs. C2 = .90) and peak exercise ST levels (NP vs. C1 = .58, NP vs. C2 = .48, C1 vs. C2 = .67). CONCLUSIONS: Concordance among raters, and with the computer-generated algorithm, was moderate to high for all parameters of EST interpretation. This study lends support to NPs interpreting ESTs.

The NO - K+ channel axis in pulmonary arterial hypertension. Activation by experimental oral therapies.

The prognosis of patients with pulmonary arterial hypertension (PAH) is poor. Available therapies (Ca(++)-channel blockers, epoprostenol, bosentan) have limited efficacy or are expensive and associated with significant complications. PAH is characterized by vasoconstriction, thrombosis in-situ and vascular remodeling. Endothelial-derived nitric oxide (NO) activity is decreased, promoting vasoconstriction and thrombosis. Voltage-gated K+ channels (Kv) are downregulated, causing depolarization, Ca(++)-overload and PA smooth muscle cell (PASMC) contraction and proliferation. Augmenting the NO and Kv pathways should cause pulmonary vasodilatation and regression of PA remodeling. Several inexpensive oral treatments may be able to enhance the NO axis and/or K+ channel expression/function and selectively decrease pulmonary vascular resistance (PVR). Oral L-Arginine, NOS' substrate, improves NO synthesis and functional capacity in humans with PAH. Most of NO's effects are mediated by cyclic guanosine-monophosphate (c-GMP). cGMP causes vasodilatation by activating K+ channels and lowering cytosolic Ca++. Sildenafil elevates c-GMP levels by inhibiting type-5 phosphodiesterase, thereby opening BK(Ca). channels and relaxing PAs. In PAH, sildenafil (50 mg-po) is as effective and selective a pulmonary vasodilator as inhaled NO. These benefits persist after months of therapy leading to improved functional capacity. 3) Oral Dichloroacetate (DCA), a metabolic modulator, increases expression/function of Kv2.1 channels and decreases remodeling and PVR in rats with chronic-hypoxic pulmonary hypertension, partially via a tyrosine-kinase-dependent mechanism. These drugs appear safe in humans and may be useful PAH therapies, alone or in combination.

Long-term outcome in patients with apical hypertrophic cardiomyopathy.

OBJECTIVES: The aim of this study was to describe long-term outcome in patients with apical hypertrophic cardiomyopathy (ApHCM) followed in a tertiary referral center. BACKGROUND: Apical hypertrophic cardiomyopathy is a relatively rare form of hypertrophic cardiomyopathy (HCM), first described in Japan. Initial reports, based on a limited number of patients, emphasized the benign nature of this condition. METHODS: A retrospective study of 105 patients with ApHCM diagnosed at the Toronto General Hospital from 1975 to 2000 was performed. Symptoms, clinical findings, mortality and cardiovascular morbidity were analyzed. RESULTS: The mean age at presentation was 41.4 +/- 14.5 years. During a mean follow-up of 13.6 +/- 8.3 years from presentation, cardiovascular mortality was 1.9% (2/105) and annual cardiovascular mortality was 0.1%. Overall survival was 95% at 15 years. Thirty-two patients (30%) had one or more major morbid events, the most frequent being atrial fibrillation (12%) and myocardial infarction (10%). Probability of survival without morbid events was 74% at 15 years. Three predictors of cardiovascular morbidity were identified: age at presentation <41 years, left atrial enlargement, and New York Heart Association (NYHA) class > or = II at baseline. Forty-four percent of the patients were asymptomatic at the time of last follow-up. CONCLUSIONS: Apical hypertrophic cardiomyopathy in North American patients is not associated with sudden cardiac death and has a benign prognosis in terms of cardiovascular mortality. Nevertheless, one third of these patients experience serious cardiovascular complications, such as myocardial infarction and arrhythmias. These data are likely to influence the counseling and management of patients with ApHCM.