The Life and Death of An American Statesman.

John Hay was born in a small mid-western town and sent by his physician father to Brown University for his education. He returned to Springfield IL where he was hired by Abraham Lincoln as a personal secretary and stayed with Lincoln through the assassination. He then returned to private life, married into a wealthy family and developed a successful literary and investment career. In 1879, he joined the State Department and later became Secretary under presidents McKinley and Roosevelt. He negotiated many important treaties including those related to building the Panama Canal. Later in life, his health deteriorated with symptoms of angina pectoris and heart failure. Limited medical understanding of these matters at the time are reviewed but were then of little benefit. Probably his most effective therapy was rest during weeks of carbonated baths at Bad Nauheim. Hay died suddenly, shortly after arriving home from the last of these trips.

Atypical Cardiac Tamponade Manifesting as Left Ventricular Diastolic Collapse: A Case Report.

Cardiac tamponade is a medical emergency, the diagnosis of which is predominantly clinical with supportive echocardiographic findings. Echocardiographic findings highly suggestive of cardiac tamponade include chamber collapse, inferior vena cava (IVC) plethora, and respiratory volume/flow variations. The right-sided cardiac chambers are a low-pressure system and are the first to show signs of collapse with high specificity for tamponade. We report the case of a 35-year-old woman who demonstrated left ventricular (LV) diastolic collapse on echocardiogram following a tricuspid valve replacement. Although left-sided chamber collapse with tamponade has been reported with localized pericardial effusions postoperatively, our patient had a large circumferential pericardial effusion. Selective chamber compression can be a presenting sign of postoperative tamponade after cardiac surgery. Our case highlights the importance of recognizing atypical forms of cardiac tamponade to help in early identification and emergent management in such patients.

The Birth of Angiotensin: An International Compromise.

Irvine Page in the United States and Eduardo Braun-Menéndez in Argentina led teams of investigators that studied the role of the kidney in blood pressure regulation. Contemporaneously in 1939, each team using different methods discovered and described a new substance now known as angiotensin. At the time of discovery, Page called it "angiotonin" and Braun-Menéndez called it "hipertensina," anglicized to "hypertensin." Over time, the importance of this substance in circulatory control, pathophysiology and pharmacology became indisputable and the need for a single name became obvious. In a remarkable accommodation, Page and Braun-Menéndez agreed to forego any claim to priority and chose a name with elements of both. Following this compromise, Page and Braun-Menéndez went on to become leaders in science in their own countries as well as recognition world-wide while, angiotensin and its derivatives have become standard components in the understanding and treatment of diseases of the heart, kidney and brain.

The Computerized ECG: Friend and Foe.

Computerized interpretation of the electrocardiogram (ECG) began in the 1950s when conversion of its analog signal to digital form became available. Since then, automatic computer interpretations of the ECG have become routine, even at the point of care, by the addition of interpretive algorithms to portable ECG carts. Now, more than 100 million computerized ECG interpretations are recorded yearly in the United States. These interpretations have contributed to medical care by reducing physician reading time and accurately interpreting most normal ECGs. But errors do occur. The computer cannot be held responsible for misinterpretations due to recording errors, such as muscle artifacts or lead reversal. But, in many abnormal ECGs, the computer makes its own errors-sometimes critical-in its incorrect detection of arrhythmias, pacemakers, and myocardial infarctions. These errors require that all computerized statements be over-read by trained physicians who have the advantage of clinical context, unavailable to the computer. Together, the computer and over-readers now provide the most accurate ECG interpretations available.

The Beat Goes On: The Story of Five Ageless Cardiac Drugs.

This article traces the history of 5 cardiac drugs-Aspirin, Atropine, Digitalis, Nitroglycerine, and Quinidine-that have been in continuous use for centuries and some for longer. Four of the 5 started life as botanicals and 4 have as also served widely varied functions far removed from their current purposes. Collectively, they have played a role in the history of royalty, religious leaders, assassinations and military campaigns in addition to their place in medical therapy. Their present clinical status has evolved from long-term clinical observation without the need for controlled clinical trials, detailed statistical analyses or FDA approvals. This review of their background illustrates the varied means by which markedly different substances from widely separated sources can come together to participate in the management of circulatory disorders.

The King Is Dead: Clark Gable's Heart Attack.

Clark Gable was born in a small Ohio mining town and never finished high school. Stage struck as a young man, he did menial jobs while working his way up to movie stardom-his most famous role was in "Gone with the Wind." He married 5 times. During WWII, he enlisted in the Army Air Corps, flew a few combat missions as a gunner and won the Distinguished Service Cross. Personally, he was intermittently obese, a drinker, smoker, hypertensive and predictably in 1960, he suffered an acute myocardial infarction. His clinical course was benign until the 10th hospital day, when he died suddenly. No resuscitation was attempted. At the time of his death, preventive cardiology, mouth-to-mouth ventilation, closed chest cardiac massage, defibrillation and coronary care units were in their infancy. The history of these and subsequent therapeutic practices are reviewed, but Gable died a bit too early for their application.

Reciprocal ST-Segment Changes in Myocardial Infarction: Ischemia at Distance Versus Mirror Reflection of ST-Elevation.

BACKGROUND: Reciprocal ST-depression in the electrocardiograms (ECGs) of patients with ST-elevation myocardial infarction (STEMI) results from either true ischemia at a distance via collateral circulation diverting blood to the infarcted region or an electrical phenomenon that results from a mirror reflection of ST-elevation. We aimed to identify the role of reciprocal ECG changes in predicting collateral circulation to the infarcted area determined angiographically. METHODS: In a retrospective study, ECG and angiography of 53 STEMI patients admitted to SUNY Upstate Medical University in 2014 were reviewed independently by experts blinded to the results of ECG and coronary angiography. RESULTS: Reciprocal changes (RC) in ECG were present in 41 patients (77%) and on angiography, 14 patients (26%) exhibited collateral vessels to the ischemic areas. No correlation was found between the presence of RC and collateral circulation (P = 0.384), or between the depth of reciprocal ST-depression and the degree of the collateral circulation (P = 0.195). However, 84% of patients without collaterals exhibited resolution of RC after successful percutaneous coronary intervention (PCI) (P = 0.036), suggesting that the ST depressions that resolved after reperfusion were directly caused by the culprit vessel. Patients without RC presented late after symptom onset (9.25 versus 3.83 hours, P = 0.004), also suggesting time related resolution. CONCLUSIONS: RC had no relation to or predictive value for collaterals on angiography. Among late presenting patients, RC were less frequent. Thus, reciprocal ST-depression may represent subendocardial ischemia from the primary coronary event or simply an electrical phenomenon, rather than ischemia at distance from impaired collateral circulation.

Hypertensive Cardiovascular Risk: Pulsatile Hemodynamics, Gender, and Therapeutic Implications.

PURPOSE: In recent years, the predictive value of 2 pulsatile parameters has been extensively studied in hypertension: aortic stiffness and pulse pressure (PP) amplification. Aortic stiffness is an index of aortic rigidity and PP-amplification is the ratio between central and brachial PP, an indirect evaluation of wave reflections. Both are safe, independent, noninvasive predictors of overall and cardiovascular risk. Our purpose is to determine the validity of these parameters in 2 different circumstances: gender and therapeutic implications. AGE EFFECT: Studies have shown that whereas steady mean arterial pressure is significantly higher in men than in women, pulsatile pressure largely predominates in women, mostly in older age and as a consequence of short stature. Gender differences require more extensive investigation due to the disparities of dose-response ranging among populations and the contribution of ethnic factors, frequently based on individual origin. REGARDING THERAPEUTIC IMPLICATIONS: Many questions have yet to be resolved. First, the prognosis of antihypertensive therapy is largely based on blood pressure reduction but also requires evaluation of arterial rigidity and wave reflections to achieve adequate therapeutic "de-stiffening." The most effective approach appears to be the combination of angiotensin- and calcium-channel blockade, in certain cases associated with diuretic compounds. Second, antialdosterone drugs can be useful, but it is their antifibrotic more than their antihypertensive effect that appears effective. Third, prevention of comorbidities, such as those associating hypertension, diabetes, and/or kidney damage, should become primary targets for drug treatment.

Accuracy of Cuff-Measured Blood Pressure: Systematic Reviews and Meta-Analyses.

BACKGROUND: Hypertension (HTN) is the single greatest cardiovascular risk factor worldwide. HTN management is usually guided by brachial cuff blood pressure (BP), but questions have been raised regarding accuracy. OBJECTIVES: This comprehensive analysis determined the accuracy of cuff BP and the consequent effect on BP classification compared with intra-arterial BP reference standards. METHODS: Three individual participant data meta-analyses were conducted among studies (from the 1950s to 2016) that measured intra-arterial aortic BP, intra-arterial brachial BP, and cuff BP. RESULTS: A total of 74 studies with 3,073 participants were included. Intra-arterial brachial systolic blood pressure (SBP) was higher than aortic values (8.0 mm Hg; 95% confidence interval [CI]: 5.9 to 10.1 mm Hg; p < 0.0001) and intra-arterial brachial diastolic BP was lower than aortic values (-1.0 mm Hg; 95% CI: -2.0 to -0.1 mm Hg; p = 0.038). Cuff BP underestimated intra-arterial brachial SBP (-5.7 mm Hg; 95% CI: -8.0 to -3.5 mm Hg; p < 0.0001) but overestimated intra-arterial diastolic BP (5.5 mm Hg; 95% CI: 3.5 to 7.5 mm Hg; p < 0.0001). Cuff and intra-arterial aortic SBP showed a small mean difference (0.3 mm Hg; 95% CI: -1.5 to 2.1 mm Hg; p = 0.77) but poor agreement (mean absolute difference 8.0 mm Hg; 95% CI: 7.1 to 8.9 mm Hg). Concordance between BP classification using the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure cuff BP (normal, pre-HTN, and HTN stages 1 and 2) compared with intra-arterial brachial BP was 60%, 50%, 53%, and 80%, and using intra-arterial aortic BP was 79%, 57%, 52%, and 76%, respectively. Using revised intra-arterial thresholds based on cuff BP percentile rank, concordance between BP classification using cuff BP compared with intra-arterial brachial BP was 71%, 66%, 52%, and 76%, and using intra-arterial aortic BP was 74%, 61%, 56%, and 65%, respectively. CONCLUSIONS: Cuff BP has variable accuracy for measuring either brachial or aortic intra-arterial BP, and this adversely influences correct BP classification. These findings indicate that stronger accuracy standards for BP devices may improve cardiovascular risk management.

Wireless: The Life and Death of Guglielmo Marconi.

With little training in physics, Guglielmo Marconi developed the invention that stunned the world by wirelessly connecting ships and continents. Ten years before his death, he sustained a myocardial infarction followed by unmistakable angina pectoris. His personality and unhappy family life limited his ability to cope with his disease and to deal with Italy's most respected physicians. But their descriptions of his diagnosis and management are surprisingly few. Poor record keeping, intentional news suppression of his failing health or limited medical opportunities could be the reason for this lack of information. He died in 1937 when the value of electrocardiograms and X-rays were recognized (he had neither), but therapeutic options were severely limited. To gain insight into his care, we compared contemporary Italian understanding of coronary heart disease to British and American teachings. When he died of an acute coronary syndrome, heart failure and dysrhythmias, he was attended only by medical staff, but by none of his large family.

The two faces of hypertension: role of aortic stiffness.

Adult hypertension can be divided into two relatively distinct forms-systolic/diastolic hypertension in midlife and systolic hypertension of the aged. The two types differ in prevalence, pathophysiology, and therapy. The prevalence of systolic hypertension in the elderly is twice that of midlife hypertension. The systolic pressure is elevated in both forms, but the high diastolic pressure in midlife is due to a raised total peripheral resistance, whereas the normal or low diastolic pressure in the elderly is due to aortic stiffening. Aortic stiffness, as measured by the carotid/femoral pulse wave velocity, has been found to be a cardiovascular risk marker independent of traditional risk factors for atherosclerosis. Instead, it is related to microcirculatory disease of the brain and kidney and to disorders of inflammation. Loss of aortic distensibility is an inevitable consequence of aging, but a review of its causes suggests that it may be amenable to future pharmacologic therapy.

Hypertension, Diabetes Type II, and Their Association: Role of Arterial Stiffness.

In patients with both hypertension and type II diabetes, the systolic blood pressure (SBP) increases linearly with age, while that of diastolic blood pressure (DBP) declines curvilinearly as early as age 45, all suggesting the development of increased arterial stiffness. Increased stiffness is an important, independent, and significant risk predictor in subjects with hypertension and diabetes. In patients with both diseases, stiffness assessed at the same mean arterial pressure (MAP) was significantly higher in diabetic patients. Arterial stiffness is related to age, heart rate (HR), and MAP, but in diabetic patients, it also related to diabetes duration and insulin treatment (IT). In the metabolic syndrome (MetSyn), diabetes also acts on the small arteries through capillary rarefaction to reduce the effective length of the arterial tree, increases the reflected pulse wave and thus the pulse pressure (PP). These studies indicate that diabetes and hypertension additively contribute to increased pulsatility and suggest that any means to reduce stiffness would be beneficial in these conditions.

The tale of infective endocarditis: fatal then curable but rarely preventable.

The story of infective endocarditis (IE) is a miracle of medical progress. In retrospect, it seems as a logical and orderly progression of remarkable events leading to the nearly complete conquest of the disease. IE was almost uniformly fatal until the 1st cures by surgery, followed by frequent cures with antibiotics, further improved when combined with valve surgery. Most recently, it has become almost a new disease with a change in the offending organisms, a change in the type of afflicted patients and the infection of implanted medical devices. Despite therapeutic success, prevention of IE has been elusive. In this review, the authors tell the story by highlighting major events, illustrating interconnections among branches of science that brought the authors to their present state and describing some well-known patients. For this summary, the authors are indebted to the more detailed descriptions of the IE history readily available for interested readers.

Assessment of aortic stiffness by transesophageal echocardiography.

BACKGROUND: Aortic stiffness, often measured by the carotid/femoral pulse-wave velocity (PWV) method, has become an attractive predictor for cardiovascular (CV) risk. Although noninvasive, PWV requires additional equipment and training. Aortic diameters measured at transesophageal echocardiography (TEE) provide high spatial resolution images as an alternative to PWV, and permit a more routine assessment of aortic stiffness. The purpose of this study was to measure aortic diameters at TEE, calculate aortic stiffness and compare these data to those of the more established PWV as estimates of CV risk and survival. METHODS: Systolic and diastolic aortic dimensions were measured retrospectively in 500 consecutive patients who had a clinically indicated TEE. Aortic compliance, distensibility, and stiffness index were calculated using the aortic diameters and corrected brachial cuff blood pressures (BP). RESULTS: Compliance significantly related to age and mean BP (both P < 0.0001) and nearly significantly to chronic renal disease (P = 0.064). The results for distensibility and stiffness index were similar. When analyzed by Kaplan-Meier curves, all stiffness tertiles were significantly predictive of 4.5- to 7.5-year survival. These calculated values behaved similar to those of PWV reported in the literature. CONCLUSIONS: This study showed that in patients undergoing routine TEE, aortic stiffness can be readily measured and that the derived values offer relationships comparable to those of PWV, including survival prediction. The method may also find use in assessing aortic stiffness in the TEE evaluation of patients with a bicuspid aortic valve or in preparation for transcatheter aortic valve replacement.

Cardiac troponins: bench to bedside interpretation in cardiac disease.

Cardiac troponins are the preferred biomarkers for the determination of acute myocardial necrosis. The high sensitivity of the available assays has significantly increased the detection of microscopic amounts of myocardial damage. Although compelling evidence indicates that elevated cardiac troponins are markers of poor prognosis and increased mortality, irrespective of the clinical scenario, small elevations can be seen in protean conditions and may confound the diagnosis of acute coronary syndromes. Emerging evidence suggests multiple different cellular mechanisms leading to cardiac troponin release, which challenge long held paradigms such as equivalency between troponin release into the circulation and irreversible cell death. Hence, knowledge of the physiology and pathophysiology of these cardiac biomarkers is essential for their accurate interpretation and consequent correct clinical diagnosis. Herein, the current relevant information about cardiac troponins is discussed, with special emphasis on pathophysiology and clinical correlates.

Hypertension and vascular dynamics in men and women with metabolic syndrome.

Metabolic syndrome (MetS), an important component of insulin resistance and cardiovascular (CV) risk, is defined by 3 or more of the following characteristics: abdominal obesity, hyperglycemia, hypertension, hypertriglyceridemia, and hypo-high-density lipoprotein cholesterolemia. Based on the previously published age- and sex-mediated DESIR (Data from an Epidemiological Study on the Insulin Resistance Syndrome) cohort and parallel central hemodynamic measurements, our goal was to evaluate the effects of MetS on brachial central pulse pressure (PP), PP amplification, aortic stiffness, and wave reflections. These data were then compared with those of patients with essential hypertension but without MetS for the same mean arterial pressure. Increased aortic stiffness, a major mechanical factor predicting CV risk, has been well identified as playing a role in MetS. Its age progression is proportional to the number of risk factors involved in MetS and is responsible for increased systolic blood pressure and decreased diastolic blood pressure with increasing age, the principal hallmarks of hypertension in the elderly. Beyond brachial pressure measurements, central hemodynamic parameters involve increased aortic stiffness, reduced wave reflections, and increased PP amplification, a parameter commonly associated with increased heart rate. With the exception of arterial stiffness, all these findings are opposite in direction to those observed in essential hypertension, in which MetS is absent. A divergent behavior of wave reflections and PP amplification, but not of arterial stiffness, is observed when hypertension is studied alone or when compared with MetS for the same mean arterial pressure. This pulsatile hemodynamic abnormality contributes independently to increase age- and sex-mediated CV risk, justifying new research regarding Framingham scores and drug treatment.