Brugada syndrome & AKAP9: Reconciling clinical findings with diagnostic uncertainty.

INTRODUCTION: Brugada Syndrome typically presents with sudden nocturnal arrhythmias. Diagnosis may be challenging due to variable and transient electrocardiogram patterns and nondiagnostic provocation studies. Genetic testing can establish the etiology, but results may be inconclusive with variants of uncertain significance. CASE: A 24-year-old male with family history of sudden cardiac death was found unresponsive due to seizure. He was hemodynamically stable. ECG showed saddle-back ST elevations in V1 and V2. Procainamide challenge was negative. We subsequently performed genetic testing, which demonstrated AKAP9 variant. DISCUSSION: AKAP9 is a scaffolding protein that facilitates phosphorylation of delayed-rectifier potassium channels. The AKAP9 variant alters potassium current causing disordered repolarization and ventricular reentry. It has been previously linked to other channelopathies, but its pathogenicity is fully undetermined. CONCLUSION: Genetic testing is a useful tool to determine the origin of channelopathy, but inconclusive results with variants of uncertain significance should be clinically correlated.

Arrythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and cathecholaminergic polymorphic ventricular tachycardia (CPVT): A phenotypic spectrum seen in same patient.

ARVD/C and CPVT are rare inheritable sudden cardiac death syndromes predominantly expressed in younger individuals. ARVD/C is characterized by a progressive fibrofatty replacement of the myocardium that predisposes to ventricular tachycardia while CPVT is characterized by exercise induced bidirectional/polymorphic ventricular tachycardia (VT) and a structurally normal heart. A mutation in different genes causes these syndromes but recently, mutation in a common gene RYR2 has been associated with both disorders and it has been suggested that CPVT and ARVD/C represent a phenotypic spectrum. We present a case unique in expressing both these phenotypes.

A rare case of hypokalemic ventricular tachycardia in a patient with thyrotoxic periodic paralysis.

Thyrotoxic periodic paralysis (TPP) is a potentially fatal complication of hyperthyroidism, characterized by recurrent muscle paralysis and hypokalemia. We present a case of a 32-year-old apparently healthy male patient, who presented with acute paraparesis associated with hypokalemia (K: 1.6 mmol/L), complicated by ventricular tachycardia (VT). Advanced cardiac life support was initiated with an amiodarone infusion, and eventually QRS complex narrowed and wide complex tachycardia resolved. Intravenous potassium chloride (KCl) 40 mEq over 2-3 h and oral KCL 40 mEq were administered to treat the electrolyte imbalance. Patient paralysis was quickly reversed; motor function was regained with movement of the lower extremities. This case highlights the importance of early recognition and prompt treatment of TPP as a differential diagnosis for muscle weakness, especially in the setting of severe hypokalemia. It is important to pay attention to the possibility of the development of lethal VT associated with hypokalemia in the setting of hyperthyroidism and thyrotoxic paralysis.

Takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy is a novel, yet well-described, reversible cardiomyopathy triggered by profound psychological or physical stress with a female predominance. OBJECTIVE: This review is designed to increase general clinician awareness about the diagnosis, incidence, pathogenesis, and therapies of this entity. DATA SOURCES: A complete search of multiple electronic databases (Pubmed, EMBASE, Science Citation Index) was carried out to identify all full-text, English-language articles published from 1980 to the present date and relevant to this review. REVIEW METHODS: The following search terms were used: takotsubo cardiomyopathy, stress-induced cardiomyopathy, and left ventricular apical ballooning syndrome. Citation lists from identified articles were subsequently reviewed and pertinent articles were further identified. RESULTS: Takotsubo cardiomyopathy is typically characterized by the following: 1) acute onset of ischemic-like chest pain or dyspnea, 2) transient apical and mid-ventricular regional wall-motion abnormality, 3) minor elevation of cardiac biomarkers, 4) dynamic electrocardiographic changes, and 5) the absence of epicardial coronary artery disease. The pathogenesis of the syndrome is unknown but has mostly been associated with acute emotional or physiologic stressors. Dote, Sato, Tateishi, Uchida, Ishihara (J Cardiol. 21(2):203-214, 1991); Desmet, Adriaenssens, Dens (Heart. 89(9):1027-1031, Sep., 2003); Bybee, Kara, Prasad, et al. (Ann Intern Med. 141(11):858-865, Dec 7, 2004); Sharkey, Lesser, Zenovich, et al. (Circulation. 111(4):472-479, Feb 1, 2005) The short and long-term prognosis of these patients is overwhelmingly favorable and often only requires supportive therapy. CONCLUSION: Whether an emotional or physical event precedes one's symptoms, it is apparent that takotsubo cardiomyopathy case presentations mimic ST-segment elevation myocardial infarction, and thus is an important entity to be recognized by the medical community.

A Case of Type I and II Brugada Phenocopy Unmasked in a Patient with Normal Baseline Electrocardiogram (ECG).

BACKGROUND Brugada pattern on electrocardiogram (ECG) is seen when there are at least 2 mm J-point elevation and 1 mm ST-segment elevation in two or more of the right precordial leads, with right bundle-branch block (RBBB)-like morphology. Elevation of a coved-type shape in leads V1 and V2 is consistent with type I Brugada pattern, whereas elevation of a saddle-back configuration distinguishes type II Brugada. If accompanied by life-threatening arrhythmias or sudden cardiac death, Brugada syndrome (BrS) is diagnosed. The presence of Brugada ECG pattern in absence of the syndrome has come to be known as Brugada phenocopy (BrP). CASE REPORT We introduce a case of both Brugada type I and II patterns unmasked in a 28-year-old female with fever secondary to mastitis. Though fever-induced BrP is a universally known phenomenon, the presentation of both type I and II patterns presenting in a patient during a single hospitalization makes this case unique from others. The patient was brought to the emergency department after experiencing a syncopal episode that appeared classically vasovagal in nature. Once her fever resolved, her baseline ECG showed no abnormalities. CONCLUSIONS Though Brugada ECG pattern may be very alarming, especially after syncope, appropriate management in the case of a fever-induced event would consist of observation with cardiac monitoring, immediate treatment of fever with antipyretics, and antibiotics for suspected infection. Close follow-up by a cardiologist as an outpatient is imperative to further ascertain if the patient is at high risk of life-threatening arrhythmias, significant for BrS.

Stroke prevention in atrial fibrillation--pharmacologic strategies.

Stroke prevention in atrial fibrillation presents a challenge for many clinicians. A considerable amount of research has gone into creating scoring systems that can accurately predict thromboembolic risk. Patients at low enough risk are best treated with aspirin, whereas higher-risk patients require anticoagulation with warfarin despite its shortcomings. Antithrombotic regimens for moderate-risk patients require careful consideration based on bleeding risk, age, and the ability to undergo frequent serum monitoring. Oral drugs may soon be available to replace warfarin. While this may simplify dosing and monitoring, it will still be necessary to weigh the risks and benefits of therapy.

Standard lipid profile.

The standard lipid profile has an enormous scientific evidence base and has provided simple clinical lipid-altering goals focused on low-density lipoprotein (LDL) cholesterol that have been shown to reduce coronary heart disease. Its limitations in estimating LDL cholesterol are well known: increasing inaccuracies in the nonfasting state, in individuals with triglycerides greater than 200 to 400 mg/dL, and as an accurate measure of LDL particle risk in size and concentration. Until studies are done comparing the benefit of targeting LDL particle concentration and size versus ever lower LDL cholesterol concentration, widespread clinical use of continuing revisions of the standard lipid profile goals will continue to remain one of the giant clinical and public health achievements of the last 50 years.

Left ventricular remodeling after myocardial infarction: past, present, and future.

Medical advances in the care of cardiac patients have resulted in more patients surviving an acute myocardial infarction (MI) than ever before. Each year hundreds of thousands of these survivors undergo remodeling of their left ventricle and often progress to clinical congestive heart failure. The extent of remodeling has been linked to the size of the infarct, whether or not the myocardium has been revascularized, and the control of loading conditions. The extent of infarction can be measured several ways, including the amount of enzyme released as well as infarct imaging with nuclear perfusion or magnetic resonance imaging. Methods to prevent adverse remodeling of the ventricle have included pharmacotherapy with beta-blockers, nitrates, and modulators of the renin-angiotensin-aldosterone system. Surgical intervention has proven useful for select patients with aneurysmal areas of remodeling. Researchers are now investigating several approaches to preventing and reversing cardiac remodeling. These include the use of stem cells to regenerate myocardium and post-infarct pacing to prevent remodeling. Improved therapies are needed to help reduce the number of patients progressing from myocardial infarction to end-stage heart failure.

Erratum: Pacing on the T Wave: PAVB, Not PVAB.

[This corrects the article on p. 94 in vol. 43, PMID: 27047297.].

The inoperable valvular heart disease patient:the pluses and minuses of percutaneous valvular replacement.

The spectrum of potentially successful treatment options for inoperable valvular disease is limited. Aortic valvuloplasty may offer temporary improvement in symptoms and some survival benefit in select non-surgical patients with aortic stenosis, but it does not improve long-term outcome. Mitral valve incompetence often responds well to surgical repair, though patients with significantly reduced left ventricular function have worsened outcomes. The design of a percutaneous implantable prosthetic heart valve is a promising alternative to valvuloplasty. Although not yet an established interventional method, Percutaneous Aortic Valve Replacement (PAVR) will likely take a position among the innovative catheter-based techniques currently in development. The appropriate clinical scenario for Percutaneous Mitral Valve Intervention (PMVI), however, may be significantly narrower. As with many other minimally invasive operations or procedures, the ethical considerations of a novel approach must be considered.

Reciprocal regulation and integration of signaling by intracellular calcium and cyclic GMP.

Calcium and guanosine-3',5'-cyclic monophosphate (cGMP) are second messenger molecules that regulate opposing physiological functions, reflected in the reciprocal regulation of their intracellular concentrations, in many systems. Indeed, cGMP and Ca2+ constitute discrete points of integration between multiple cell signaling cascades in both convergent and parallel pathways. This chapter describes the molecular mechanisms regulating intracellular Ca2+ and cGMP, and their integration in specific cellular responses.