Ticagrelor Does Not Protect Isolated Rat Hearts, Thus Clouding Its Proposed Cardioprotective Role Through ENT 1 in Heart Tissue.

P2Y12 receptor-blocking drugs given at reperfusion offer protection against myocardial infarction in animal models of transient coronary occlusion. Two recent reports concluded that ticagrelor was more cardioprotective than clopidogrel and attributed this to ticagrelor's unique ability to raise tissue adenosine by blocking the equilibrative nucleoside transporter 1. Indeed, an adenosine receptor blocker attenuated ticagrelor's protection. The related P2Y12 inhibitor cangrelor, which does not block the transporter, protects hearts only when platelets are in the perfusate, while adenosine is known to protect equally in situ blood-perfused and crystalloid-perfused isolated hearts. We, therefore, tested whether ticagrelor liberates a sufficient amount of adenosine to protect a Krebs buffer-perfused isolated rat heart subjected to 40 minutes of global ischemia followed by 2 hours of reperfusion. In untreated hearts, 77.6% ± 4.0% of the ventricle was infarcted as measured by triphenyltetrazolium staining. Ischemically preconditioned hearts had only 32.7% ± 3.6% infarction ( P < .001 vs untreated), indicating that our model could be protected by preconditioning which is known to involve adenosine. Strikingly, hearts treated with 10 µmol/L ticagrelor in the buffer throughout the reperfusion period had 77.5% ± 2.4% infarction comparable to unprotected controls ( P = NS vs untreated). These data strongly suggest that ticagrelor was unable to release sufficient adenosine from the crystalloid-perfused rat heart to protect it against infarction. Our previous studies have found no difference in the anti-infarct potency among clopidogrel, cangrelor, and ticagrelor in open-chest rats and rabbits, and surprisingly adenosine receptor antagonists block protection from all 3 drugs. We have no explanation why ticagrelor is more protective in the pig than clopidogrel but suspect a species or perhaps a treatment schedule difference that may or may not involve adenosine.

Thyrotoxic Valvulopathy: Case Report and Review of the Literature.

We report a 42-year-old female who was admitted for abdominal pain, and also endorsed dyspnea, fatigue and chronic palpitations. Past medical history included asthma, patent ductus arteriosus repaired in childhood and ill-defined thyroid disease. Physical examination revealed blood pressure of 136/88 mm Hg and heart rate of 149 beats per minute. Cardiovascular exam revealed an irregularly irregular rhythm, and pulmonary exam revealed mild expiratory wheezing. Abdomen was tender. Electrocardiogram revealed atrial fibrillation with rapid ventricular response which responded to intravenous diltiazem. Labs revealed TSH of < 0.1 mU/L and free T4 of 2.82 ng/dL, a positive TSH-receptor and thyroid peroxidase antibodies suggesting Grave's thyrotoxicosis. A transthoracic echocardiogram reported an ejection fraction of 55-60%, with mild to moderate mitral regurgitation (MR) and moderate to severe tricuspid regurgitation (TR) and dilated right heart chambers. Pulmonary artery systolic pressure was 52 mm Hg. Transesophageal echocardiogram revealed a myxomatous tricuspid valve with thickening and malcoaptation of the leaflets and moderate to severe TR, mild to moderate MR with mild thickening of the mitral valve leaflets. Abdominal ultrasound revealed wall thickening of the gall bladder concerning for acute cholecystitis. She underwent laparoscopic cholecystectomy and was discharged in stable condition on methimazole for her thyroid disease, and on oral diltiazem for rate control and anticoagulation for atrial fibrillation. Follow-up visit with her cardiologist few months later documented absence of cardiac symptoms, and no murmurs were reported on physical examination. This case underscores the importance of maintaining a high index of suspicion for hyperthyroidism when faced with significant newly diagnosed pulmonary hypertension and TR, as treatment of the thyroid abnormalities can reverse these cardiac findings.

Chest Pain With Apical Diverticulum in the Absence of Coronary Disease: Case Report and Review of the Literature.

Aneurysmal dilatation of segment of the left ventricle in the absence of coronary disease has been reported and termed diverticulum, which appears to be a congenital anomaly. A 56-year-old white female was admitted to our hospital with chest pain that has been intermittent over the past 1 month. The pain was described as exertional, substernal and pressure-like in quality, radiating to left arm and jaw, and lasting approximately 30 minutes each episode; it was associated with shortness of breath. She has had approximately 10 such episodes in the past 1 month. The patient denied any dizziness, palpitations, syncope, orthopnea or paroxysmal nocturnal dyspnea (PND). She has had a history of hypertension for many years, however has not been compliant with her medications for the past 6 months. On admission, vital signs revealed blood pressure of 185/100 mm Hg, and regular heart rate of 94 beats per minute. Physical examination revealed a normal body habitus. Cardiac examination revealed no murmurs or extra cardiac sounds on auscultation. The pulmonary and abdomen examinations were unremarkable. The chest radiograph was normal. The electrocardiogram showed sinus rhythm, with borderline prolongation of the QT interval. The laboratory test results, including cardiac enzymes, were normal. Transthoracic echocardiography (TTE) revealed normal left ventricular systolic function, with localized dyskinesis of the apex. No significant valvular abnormalities were identified. Coronary angiography revealed angiographically normal coronary arteries; left ventriculography showed abnormal apical "filling defect" consistent with an aneurysm. A repeat echocardiogram using Definity contrast revealed left ventricular apical diverticulum with hypertrabeculation. The patient was placed on antihypertensive medications with resolution of her chest pain, and was able to ambulate comfortably. The patient was counseled thoroughly on the importance of compliance with her medications. This case describes an apical left ventricular diverticulum found incidentally and demonstrated on contrast echocardiography in a patient with chest pain.