You've gotta have heart!


  • Potential conflict of interest: Nothing to report.

“See boys, that's what I'm talking about. Baseball is only half skill, the other half is something else… something bigger!”

With this uplifting allusion to the virtues of determination, motivation, optimism and bravado, — in short “heart”, in the emotional sense — the coach of an underdog baseball team begins the show-stopping song and dance anthem of the 1950's Broadway success Damn Yankees! The catchy song title that introduces and inspired this month's Landmark In Hepatology, is used to focus attention on the importance of the heart to the well-being of the liver, in the anatomical and physiological sense. But first let us linger for a moment with Broadway and Baseball, two of America's long-standing and most recognizable cultural emblems. In the 1950s, playwright George Abbott collaborated with author Douglass Wallop, who wrote the original story “The Year the Yankees Lost the Pennant”,1 to transform Wallop's book into a Faustian musical play about baseball. The fruit of their efforts, the production Damn Yankees!, which extolled the conservative values of Eisenhower's America, won Tony Awards in 1956 for Best Authors (of a musical) and Best Musical. Joe Boyd, an aging, fanatically-devoted supporter of the Washington Senators, sells his soul to the Devil in the likeness of the sulfurous Mr. Applegate, so as to be incarnated as the youthful player Joe Hardy for the last 2 months of the baseball season. The plot is for heroic Joe to help his hapless team wrestle the coveted baseball pennant from the all-conquering men in pinstripes, the New York Yankees. Though there have been innumerable essays, articles, books, plays, documentaries and movies about baseball, this Broadway beacon with its unfashionable sentiments of nostalgia, homesickness, guilt over deception, and resistance to temptation, has been revived several times over the past 50 years. The story exemplifies the quasi-religious esteem that the quintessentially American game of baseball has had in the culture of the United States for over 150 years, along with other patriotic icons like Mother and Apple Pie.

To the newcomer to the United States, and to the relative newcomer like the author who has been here for almost 26 years and counting, the appeal of baseball can be bewildering with its arcane rules and strategies, oft-intoned mind-boggling statistics, quaint pajama-like uniforms, and unfathomable hand gestures and jargon. For example, how can a baseball competition be called a “World Series”, when the rest of the world does not participate? Yet, despite the setbacks of financial misdemeanors, players' strikes, accusation of body-building hormone use, and exorbitant salaries, baseball even enticed a scholarly past president of Yale University, Angelo Bartlett Giamatti, to be its Commissioner (1986-1989) until his untimely death. Best remembered as the Commissioner who oversaw the banishment from the sport of the popular player Pete Rose for his gambling infractions of 1989, Bart, as he was affectionately called, embodied the appeal and romance that baseball has for Americans of every stripe. Given the loyalty and passion that the National Pastime evokes, not to mention the millions of dollars that are lavished on its players, it is hardly surprising that fierce debate and fervent research continue on the beginnings of the sport and, in particular, whether it was an original American creation, as many hope and believe, or it simply evolved from other bat and ball games that were popular in the Old World and in the colonies.2 When questioned, many a red-blooded American will repeat the legend that General Abner Doubleday invented the game of baseball in Cooperstown, New York, on an inspired day in 1839. Neither that this hero of Gettysburg and other Civil War battles, and later mystic, spiritualist, occultist and onetime President of the American Theosophical Society, scarcely could have been the game's Creator, nor the recorded fact that baseball had been played in England a century or more earlier,3, 4 have been sufficiently compelling reasons either to dispel the Doubleday myth entirely or to have prevented the establishment of the Baseball Hall of Fame and Museum of Baseball in Cooperstown, New York in 1939, on the centennial of the game's supposed creation there. Incidentally, for those who wonder, it is equally unlikely that baseball was derived from the English games of “rounders” or “feeder” either.2 Musing on the origin of baseball, the late Stephen Jay Gould, eminent evolutionary biologist, philosopher, and writer, surmised that baseless creation myths are often preferred by humanity to evolutionary stories,5 as the current debate in the United States over the relative merits of teaching Darwinian Evolutionary Theory and what is glibly being termed “Intelligent Design”, bears witness.

In contrast to the obvious importance that heart has, in the sentimental sense, to the welfare of baseball, the importance of the heart physiologically to the well-being of the liver has been, relatively speaking, relegated to a minor league as the prevalence of rheumatic heart disease and prolonged heart failure has waned, certainly compared to more fashionable liver disorders like alcoholic liver disease, viral hepatitis, autoimmune liver disease, hemochromatosis and even rarities like Wilson disease — all of which have been recognized with articles in this Landmarks series. The relationship between the liver and the heart has never been a close one, however, notwithstanding the facts that these organs uniquely have dual circulations (as does the pituitary too, it turns out), are closely connected through a very short conduit of vena cava, and are intimately juxtaposed on either side the diaphragm (Fig. 1). Admittedly, the heart resides in the lofty aerated thorax, which Thomas Vicary referred to as the “Arke or Chest of the spiritual members of man,”6, 7 whereas the liver is stowed away in the lowly abdomen together with organs of excretion. Call it what you will, bitter-sweet, love-hate or Yin-Yang, the liver and heart have an oxymoronic relationship at best, perhaps dating from the apotheosis of the heart during the Renaissance. In antiquity, the body was thought to be hepatocentric, when the liver was not only considered to be the origin of the veins and the factory of the blood,8 but also the seat of the soul.9 However, the liver lost its preeminence once the circulation of the blood was discovered and a cardiocentric view of the body, which Aristotle had espoused two millennia earlier, took sway. When both organs are performing well, they are seemingly oblivious of one another, but when one fails or is dysfunctional, the other is likely to suffer. Cirrhosis and portal hypertension dilate the vasculature,10 cause the heart to beat harder and faster,11 raise the pressure in the pulmonary vascular tree,12 interfere with both systolic13, 14 and diastolic function,15 and even meddle with ventricular depolarization by decreasing conductance of potassium channels to prolong the Q-T interval.16 By way of reciprocation, when there is cardiac misbehavior the liver feels the brunt, irrespective of whether it is the left heart or the right heart that is at fault, or both.

Figure 1.

The liver supports the heart and, at the same time, is suspended from it. The Yin-Yang of liver and heart, as depicted by legendary medical artist Frank H. Netter, MD. From the Ciba Collection of Medical Illustrations Volume 3. A compilation of paintings on the normal and pathologic anatomy of the digestive system. Part III. Liver, Biliary Tract and Pancreas. With a supplement on new aspects of structure, metabolism, diagnostic and surgical procedures associated with certain liver diseases. Prepared by Frank H. Netter, MD. Edited by Ernst Oppenheimer, MD. 2nd Edition. Commissioned and published by CIBA Pharmaceutical Company, Division of Ciba-Geigy Corporation. New York. 1964. Reproduced with permission from Novartis.

Whereas Withering's patient whose dropsy was cured by drinking Foxglove tea17 undoubtedly had passive congestion of the liver, the credit for being the first to document hepatic venous congestion, such as that caused by congestive heart failure, must surely go to Francis Kiernan. In the classic monograph in which he defined the hexagonal liver lobule and was the first to identify portal tracts (portal triads),18 Kiernan also reported the macroscopic changes that occur in the hepatic venous congested liver, as seen by the naked eye or with a hand lens after dissection with or without injecting mercury or gelatin into its various blood vessels and ducts. He used the term “nutmeg liver” to describe the exaggerated appearance of the lobular architecture, in which dark central zones and pale peripheries give a mottled appearance that is typical of advanced hepatic venous congestion. To the anatomist of the early 19th Century, a section of the congested liver resembled the cut surface of the popular seed kernel of the fruit of the nutmeg tree Myristica fragrans, from the Dutch East Indies, which had been the king of spices in England for two hundred years or so, and the cause of many an international conflict since the earliest days of the 17th Century.19 Strange to relate, Kiernan thought that passive congestion of the liver was a natural occurrence after death because of the dual hepatic venous circulation, and he did not discuss pathological causes, such as heart failure, in his compulsively detailed anatomical report. Yet passive congestion of the liver and Kiernan's nutmeg cognomen were soon widely regarded as consequences of hepatic venous hypertension due to congestive heart failure, mitral and tricuspid valve disease, pulmonary afflictions, and the like.20–24 Ultimately it was accepted that pericentral fibrosis and true cardiac cirrhosis could follow prolonged passive hepatic venous congestion alone,25–27 without the need for synergistic factors like alcohol or other toxins.20, 28, 29 On the other hand, Charles Murchison's hypothesis seems far fetched, namely that the ingestion of food that “errs in being habitually too rich in quality or in excessive quantity may cause congestion of the liver” and that this is “more likely… in weakly persons who live indolent and sedentary lives, than in persons of a robust constitution who take plenty of muscular exercise in the open air”.21 One must surely doubt his inferential powers too if he truly believed what he wrote, that “congestion of the liver, and even cirrhosis, follow a successful operation for piles21, (i.e., hemorrhoids).

Once it was appreciated that one form of hepatic circulatory insufficiency, namely passive hepatic-venous congestion, had a fairly uniform deleterious effect on the liver irrespective of the primary cause, one would have thought that liver damage due to a complementary failure of the hepatic circulation, namely poor liver perfusion, would have been recognized soon. But, somehow, it took clinicians, clinical scientists, physiologists, and pathologists several decades to discover hepatic ischemia. A clue had been given by Kiernan when he described a pattern of lobular darkness and pallor that was the reverse of that seen in hepatic-venous congestion, and which he called “portal-venous congestion”.18 This was a rare finding and though the observation was echoed by others,20 no useful ideas on etiology or pathogenesis were forthcoming then.

The effect of oxygen deprivation on the integrity of hepatocytes was investigated in the early years of the 20th Century.30 The conclusion was that low oxygen tension in the blood rather than reduced oxygen delivery is the key factor that leads to ischemic hepatic necrosis when there is hypoxemia,30–32 with contributions due to diminished hepatic blood flow and hepatic venous congestion, especially if the latter is severe as may occur in advanced right heart failure and constrictive pericarditis.33 From the 1950s, the list of causes of acute ischemic liver injury was extended to include myocardial infarction34, 35 and cardiogenic shock,36 left ventricular and biventricular failure,33, 37, 38 and other reasons for shock like sepsis, acute pancreatitis, peritonitis, trauma, blackwater fever and following major surgery.39–42 Centrizonal necrosis was the predominant histological lesion of hepatic ischemia in most series of cases in which liver histology was available,31–38, 43 occasionally midzonal necrosis occurs too,33, 44 whereas sinusoidal changes likely reflect concomitant passive congestion.33, 45 The diagnosis maybe inferred when there is an abrupt and significant elevation of aminotransferases,31, 35–38, 46–51 usually without much in the way of alkaline phosphatase induction, and usually followed by normalization within 7-10 days.52, 53 In the context of the theme of the Yin-Yang of the liver-heart relationship, it is ironic to reflect that the serum enzyme activity assay that, as a medical student, Arthur Karmen devised for the diagnosis of acute myocardial infarction, the serum glutamic oxaloacetic transaminase54, 55 (SGOT, now known as serum aspartate aminotransferase, AST), should have been quickly applied to testing the liver56 and adopted by hepatologists57 and then abandoned by the cardiologists.58

The diagnosis of hepatic ischemic damage is usually easy in the typical clinical setting and with the characteristic laboratory findings just described.52, 53 On occasion, the clinical picture of liver injury and even liver failure overshadow the cause of hepatic ischemia, and patients may present in a fulminant fashion,59–62 even without apparent cardiac dysfunction.63 More than a Century ago, Victor Charles Hanot coined the colorful term “hepatic asystole” for cases in which the hepatic disease eclipses the primary cardiac disorder.64 It is noteworthy that liver failure can occur as a reversible phenomenon in patients with chronic heart disease when there is a transient deterioration in circulatory failure.62 Indeed, it has recently been argued that ischemic liver damage only occurs with shock in patients who have underlying right heart failure and resulting hepatic venous congestion that predisposes the liver to hypotensive injury, by a number of proposed mechanisms.53 Whether brief periods of hepatic ischemia are actually beneficial in protecting the liver from subsequent reperfusion injury,53 is another question.65

One of the best and most useful series of examples of hepatic asystole, is the mimicry of acute viral hepatitis by inapparent left ventricular failure.66 This brief report has always been a landmark in hepatology for the author — who has given generations of trainees reprints of the article — because of the frequency with which this often unrecognized phenomenon is encountered in clinical practice, especially in patients who are being evaluated for cardiac surgery or heart transplantation. Cohen and Kaplan reported the cases of 4 patients in whom an initial diagnosis of hepatitis was made because of striking aminotransferase elevations that were either prolonged or only resolved when the hitherto unsuspected cardiac cause was treated.66 Each of the patients was subsequently shown to have central hepatic necrosis associated with critical left ventricular failure, but there was no hypotension or sign of right heart failure, and there were no recognized symptoms or signs of cardiac decompensation when the diagnosis of a hepatitis-like illness was entertained. This phenomenon is not restricted to adults, as similar cases have been encountered in adolescents too.67 A low threshold for considering the diagnosis and prompt evaluation by cardiac catheterization and transjugular liver biopsy can avoid unwarranted delays in appropriate cardiac therapy, including surgery.

In ending this romp through the disease interactions of the heart and the liver, prompted by musings over baseball, mention must be made of the ultimate heart-liver rivalry where each organ is sufficiently diseased to justify its own transplantation, but the latter is precluded by severe disease in the other organ. For such dire circumstances, the Draconian solution is to extirpate and replace both organs in the formidable procedure of double transplantation, which offers a reasonable chance of survival (80% and 70% at 1 and 3 years, respectively), if organs can be found expeditiously.68 But let us close as we began, by considering again the role of the heart in the National Pastime of baseball, and where better to turn than to the words of Bart Giamatti, of Andover, Princeton and Yale, and 7th Commissioner of Major League Baseball in the United States. He said “It breaks your heart”. “It is designed to break your heart, the game begins in the Spring when everything else begins again, and it blossoms in the Summer, filling afternoons and evenings, and then as soon as the chill rains come, it stops and leaves you to face the Fall alone”. Who says that scholarship and letters are wasted on sport?


The author acknowledges the indispensable help of Margie Myers for her continuing efforts in literature retrieval and manuscript preparation.