Absence Of Epicardial Coronary Disease Research Articles

Myocardial Perfusion Defects in Hypertrophic Cardiomyopathy Mutation Carriers.

BackgroundImpaired myocardial blood flow (MBF) in the absence of epicardial coronary disease is a feature of hypertrophic cardiomyopathy (HCM). Although most evident in hypertrophied or scarred segments, reduced MBF can occur in apparently normal segments. We hypothesized that impaired MBF and myocardial perfusion reserve, quantified using perfusion mapping cardiac magnetic resonance, might occur in the absence of overt left ventricular hypertrophy (LVH) and late gadolinium enhancement, in mutation carriers without LVH criteria for HCM (genotype‐positive, left ventricular hypertrophy‐negative).Methods and ResultsA single center, case‐control study investigated MBF and myocardial perfusion reserve (the ratio of MBF at stress:rest), along with other pre‐phenotypic features of HCM. Individuals with genotype‐positive, left ventricular hypertrophy‐negative (n=50) with likely pathogenic/pathogenic variants and no evidence of LVH, and matched controls (n=28) underwent cardiac magnetic resonance. Cardiac magnetic resonance identified LVH‐fulfilling criteria for HCM in 5 patients who were excluded. Individuals with genotype‐positive, left ventricular hypertrophy‐negative had longer indexed anterior mitral valve leaflet length (12.52±2.1 versus 11.55±1.6 mm/m2, P=0.03), lower left ventricular end‐systolic volume (21.0±6.9 versus 26.7±6.2 mm/m2, P≤0.005) and higher left ventricular ejection fraction (71.9±5.5 versus 65.8±4.4%, P≤0.005). Maximum wall thickness was not significantly different (9.03±1.95 versus 8.37±1.2 mm, P=0.075), and no subject had significant late gadolinium enhancement (minor right ventricle‒insertion point late gadolinium enhancement only). Perfusion mapping demonstrated visual perfusion defects in 9 (20%) carriers versus 0 controls (P=0.011). These were almost all septal or near right ventricle insertion points. Globally, myocardial perfusion reserve was lower in carriers (2.77±0.83 versus 3.24±0.63, P=0.009), with a subendocardial:subepicardial myocardial perfusion reserve gradient (2.55±0.75 versus 3.2±0.65, P=<0.005; 3.01±0.96 versus 3.47±0.75, P=0.026) but equivalent MBF (2.75±0.82 versus 2.65±0.69 mL/g per min, P=0.826).ConclusionsRegional and global impaired myocardial perfusion can occur in HCM mutation carriers, in the absence of significant hypertrophy or scarring.

Epicardial coronary stenosis severity and myocardial perfusion

Patients suspected of having epicardial coronary disease are often investigated with noninvasive myocardial ischemia tests to establish a diagnosis and guide management. However, the relationship between myocardial ischemia and coronary stenoses is affected by multiple factors, and there is marked biological variation between patients. The ischemic cascade represents the temporal sequence of pathophysiological events that occur after interruption of myocardial oxygen delivery. The earliest part of the cascade is examined via perfusion imaging, and fractional flow reserve (FFR) is a corresponding index which is specific to the coronary artery. Whereas FFR has come to be regarded a clinical reference standard against which other newer invasive and noninvasive tests are validated, the diagnostic FFR threshold for detecting ischemia was established against a combination of noninvasive ischemia tests that assessed different stages of the ischemic cascade. Moreover, the validity of invasive pressure-derived indices of stenosis severity are contingent on the assumption that pressure is proportional to flow if microvascular resistance is constant, a condition induced by pharmacological intervention or by examining specific segments of the cardiac cycle. Furthermore, myocardial perfusion reserve depends on dynamic modulation of microvascular resistance, and dysfunction of the microvasculature can lead to ischemia even in the absence of epicardial coronary disease.

Abstract 13903: When an Octopus Acts Like a Chameleon: a Case of Takotsubo’s Cardiomyopathy with Concurrent Severe Coronary Disease

Introduction: Takotsubo’s cardiomyopathy, or stress induced cardiomyopathy, is characterized by transient wall-motion abnormalities involving the left ventricular apex and mid-ventricle in the absence of obstructive epicardial coronary disease. It is seen more commonly in post-menopausal women and is usually preceded by an acute medical illness or intense emotional or physical stress. While the Mayo Criteria for the classification of Takotsubo’s cardiomyopathy involves the absence of epicardial coronary disease, up to 10% of patients have been found to have concurrent significant coronary artery disease. Conclusions: We present a case of a patient who presented with seizures and was found to have ST elevations, elevated cardiac enzymes and a new cardiomyopathy. While it was discovered that she had severe coronary disease of her LAD and RCA, the true nature of her cardiomyopathy and presentation was a stress-induced cardiomyopathy in the setting of seizure. The accuracy of this diagnosis affected the prognosis and treatment options for our patient. Cardiac MRI, and specifically the presence or absence of late gadolinium enhancement, helped differentiate the etiology of her cardiomyopathy. With the increasing prevalence of coronary disease, we will likely see more cases such as these in the future and should continue to evolve our definition and tools for the diagnosis of an increasing and interesting phenomenon.

Symptoms in Patients With Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction: Is It All About Diastole?

Although it has been ≈50 years since Ross and Braunwald1 reported the malignant natural history of aortic stenosis (AS) after the onset of angina, syncope, or heart failure, the pathophysiologic underpinnings of these classic symptoms remain incompletely delineated. We appreciate that angina may occur in the absence of epicardial coronary disease with both increased demand and impaired supply, contributing to imbalance of the supply–demand relationship. Exertional syncope reflecting the inability to maintain cerebral perfusion is attributed to an inability to increase cardiac output in combination with, at times, paradoxically reduced systemic vascular resistance. Although we attribute the low-output symptoms of heart failure to the same inability to increase cardiac output, we still have an incomplete understanding of the changes that restrict stroke volume augmentation. Similarly, although the dyspnea of heart failure is typically linked to elevated pulmonary capillary pressures, which of the multiple pathways leading to elevated pulmonary pressures is/are operative in the symptomatic patient with AS? Although afterload mismatch and attendant left ventricular (LV) systolic dysfunction provide a substrate for symptoms in some patients, understanding the basis for symptoms in patients with preserved LV ejection fraction (EF) is particularly challenging because measures of AS severity alone predict the onset of but correlate imperfectly with the presence of symptoms.2 Article see p 142 In this issue of Circulation: Cardiovascular Imaging , Dahl et al3 provide hypothesis-generating data that argue an important role for LV remodeling and diastolic dysfunction in the pathogenesis of symptoms in patients AS and preserved (≥50%) LVEF. They compared echocardiographic parameters in 139 asymptomatic patients assessed in an outpatient clinic and 99 symptomatic patients referred for surgical intervention. Although the symptomatic patients were surprisingly younger, had less atrial fibrillation, hypertension, and chronic lung disease than did the asymptomatic cohort, higher LV mass index and …

Cardiovascular Effects of Cocaine

The use of cocaine has evolved from chewing the leaves of the Erythroxylon coca bush thousands of years ago, to purification of cocaine hydrochloride over 100 years ago and its use in tonics and elixirs (at one time in popular cola drinks), to insufflating and injecting the fine, white, water-soluble, powder form, to a smokable freebase form called “crack,” which became popular in the 1980s.1 In 2007, 2.1 million Americans had recent cocaine use; 1.6 million met criteria for cocaine dependence or abuse.1 Cocaine accounted for 31% of all visits to the emergency department related to drug misuse or abuse.1 From 1971 to 1987, the incidence of deaths caused by cocaine overdose increased 20-fold in Dade County, Florida.2 In a consecutive series of 233 emergency visits by cocaine-using patients, 56% presented with cardiovascular complaints, including 40% with chest pain.3 A minority of these patients have acute myocardial infarction (MI) (≈6%),4,–,7 and overall mortality is low (<1%).3,–,5,8,–,10 However, cocaine is associated with a number of cardiovascular diseases, including MI, heart failure, cardiomyopathies, arrhythmias, aortic dissection, and endocarditis. Identifying patients with acute disease is challenging. This review describes the relationship between cocaine and various cardiovascular diseases, as well as appropriate diagnostic evaluation and therapies. ### Molecular Cocaine stimulates the sympathetic nervous system by inhibiting catecholamine reuptake at sympathetic nerve terminals,11,12 stimulating central sympathetic outflow,11 and increasing the sensitivity of adrenergic nerve endings to norepinephrine (Figure 1).12 Cocaine also acts like a class I antiarrhythmic agent (local anesthetic) by blocking sodium and potassium channels, which depresses cardiovascular parameters.13 Of these 2 primary, opposing actions, enhanced sympathetic activity predominates at low cocaine doses, whereas the local anesthetic actions …

Cardiogenic Shock Complicating Subarachnoid Haemorrhage Diagnosed as Tako Tsubo Cardiomyopathy: A Cautionary Tale

Tako Tsubo or "stress" cardiomyopathy and its variants are well recognised as potential causes of acute coronary presentations, with manifestations including chest pain, cardiac failure and arrhythmia. Similarly, subarachnoid haemorrhage may be associated with cardiac abnormalities. Tako Tsubo cardiomyopathy is a diagnosis of exclusion with typical left ventricular dysfunction in the absence of epicardial coronary disease, but importantly also after exclusion of an intracerebral insult. We describe a case of unrecognised intracerebral haemorrhage with left ventricular dysfunction consistent with both variant Tako Tsubo cardiomyopathy and subarachnoid haemorrhage in a patient treated with intra-aortic balloon pump counterpulsation and associated heparinisation.

Hypertensive Heart Disease

Hypertensive heart disease encompasses anatomical changes and altered physiology of heart muscle, coronary arteries, and great vessels. Left ventricular hypertrophy is not only a target organ response to increased afterload, but is also the most potent cardiovascular risk factor. Regression of hypertrophy reduces morbidity and mortality. Heart failure may be present in the absence of a reduction of myocardial contractility. Ischemic heart disease occurs in the absence of epicardial coronary disease. Left atrial size and atrial fibrillation are associated. Potentially lethal ventricular arrhythmias and sudden cardiac death are more common in hypertensive patients. The relationship of aortic root size to blood pressure is weaker than expected; however, the relationship to aortic dissection is stronger. Careful attention and treatment of left ventricular hypertrophy, heart failure, ischemic heart disease, and atrial fibrillation will improve survival.

Increased TIMI frame counts in cocaine users: a case for increased microvascular resistance in the absence of epicardial coronary disease or spasm.

Cocaine produces adverse cardiovascular effects, some of which cannot be explained by epicardial coronary artery disease (CAD) or spasm. The hypothesis of this study was that cocaine users would have increased coronary microvascular resistance, even in the absence of recent myocardial infarction (MI), CAD, or spasm. Microvascular resistance was assessed by the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (cTFC) method in a consecutive series of 59 cocaine users without acute or recent MI or angiographically significant epicardial stenosis (> 50%) or spasm. The cTFCs in these patients were compared with 21 normal controls and with published normal cTFC values. The cTFC was significantly elevated (by 26-54%) in cocaine users. The cTFCs in the left anterior descending (LAD), circumflex (LCx), and right coronary (RCA)arteries in cocaine users were 30.0 +/- 10.9,34.1 +/- 11.5, and 28.6 +/- 11.8, respectively, compared with values in normal controls of 21.3 +/- 4.3 (p = 0.001), 24.4 +/- 7.2 (p = 0.001), and 22.7 +/- 5.1 (p = 0.04), respectively, and published normal cTFC values (all p < 0.01). An abnormally high cTFC was present in 61% of patients in the LAD, 69% in the LCx, and 47% in the RCA. Markedly decreased coronary blood flow velocity, indicating increased microvascular resistance, is present in cocaine users, even in the absence of acute or recent MI, or significant epicardial CAD or spasm. Increased microvascular resistance may explain many important cardiovascular manifestations of cocaine use and has therapeutic implications. Slow coronary filling may also suggest the possibility of cocaine use in patients in whom it was not otherwise suspected.

New concepts in diastolic dysfunction and diastolic heart failure: Part II: causal mechanisms and treatment.

As described in Part I of this 2-part article,1 diastolic heart failure is common and causes significant alterations in prognosis. In Part II, experimental studies that have provided insight into the mechanisms that cause diastolic heart failure will be described.2–19⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓ In addition, current treatment strategies and the design of future clinical trials of diastolic heart failure will be discussed. The development of truly effective therapy for diastolic heart failure depends on gaining a clear understanding of the basic mechanisms that alter diastolic function and the ability to efficiently target these mechanisms to correct these abnormalities in diastolic function. Conceptually, the mechanisms that cause abnormalities in diastolic function that lead to the development of diastolic heart failure can be divided into factors intrinsic to the myocardium itself (myocardial) and factors that are extrinsic to the myocardium (extramyocardial; Table 1). Myocardial factors can be divided into structures and processes within the cardiac muscle cell (cardiomyocyte), within the extracellular matrix (ECM) that surrounds the cardiac muscle cell, and that activate the autocrine or paracrine production of neurohormones. Each of these mechanisms are active in the major pathological processes that result in diastolic dysfunction and heart failure. Myocardial and extramyocardial mechanisms, cellular and extracellular mechanisms, and neurohumoral activation each play a role in the development of diastolic heart failure caused by ischemia, pressure-overload hypertrophy, and restrictive and hypertrophic cardiomyopathy. View this table: Table 1105290. Diastolic Heart Failure: Mechanisms ### Cardiomyocyte Diastolic dysfunction can be caused by mechanisms that are intrinsic to the cardiac muscle cells themselves. These include changes in calcium homeostasis caused by (1) abnormalities in the sarcolemmal channels responsible for short- and long-term extrusion of calcium from the cytosol, such as the sodium calcium exchanger and the calcium pump; (2) …

Significance of positive or negative thallium-201 scintigraphy in hypertrophic cardiomyopathy

Myocardial ischemia, fibrosis and infarction may occur in patients with hypertrophic cardiomyopathy (HC) in the absence of epicardial coronary artery disease. To determine their prevalence and relation with common characteristics, stress thallium-201 scintigraphy was performed in 28 patients. Eleven (39%) had positive scans despite normal epicardial coronary arteries (7 patients) or a pretest risk of coronary disease ≤5% (4 patients). There was no relation between thallium defects and age, sex, chest pain or outflow tract gradients at rest. However, the mean left ventricular ejection fraction was significantly lower in those with perfusion abnormalities compared with those without (64 ± 15 vs 75 ± 11%, respectively, p < 0.05). Also, the mean ventricular septal thickness was greater in patients with positive scans (27 ± 7 vs 21 ± 6 mm, p < 0.05), and there was a nonparametric relation between increasing septal thickness and the frequency of positive scans (p < 0.025). Seven of 11 patients with positive scans had ventricular tachycardia compared with none among those who had negative scans (p < 0.001), and 5 of these 11 patients had conduction system disease requiring permanent pacemaker insertion compared with 1 of 17 with negative scans (p < 0.025). It is concluded that thallium perfusion abnormalities are common in patients with HC in the absence of epicardial coronary disease, and are strongly associated with potentially lethal arrhythmias. Thallium scintigraphy appears to identify a subset of patients with HC at increased risk for sudden death, who therefore require closer follow-up.