Historical Article

HIGH ALTITUDE MEDICINE & BIOLOGY Volume 15, Number 4, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/ham.2014.1047

Dilated Hearts at High Altitude: Words From On High Harvey V. Lankford, MD, FACE,1 and Erik R. Swenson, MD2

Abstract

Lankford, Harvey V, Erik R Swenson. Dilated hearts at high altitude: Words from on high. High Alt Med Biol 15:000–000, 2014.—From the time of the turn of the twentieth century, dilated hearts and presumed cardiac fatigue in expeditionary climbers and scientists have been the subject of much commentary in the medical and mountaineering literature. Although largely attributed by most, but not all, to left heart strain, the description of dilated hearts in these accounts is clearly that of right heart dilation as a consequence of high and sustained hypoxic pulmonary vasoconstriction with hypertensive remodeling. This essay will feature quotations from the writings of high altitude pioneers about dilated, strained, or enlarged hearts. It will give some brief physiology of the right side of the heart as background, but will focus on the words of mountaineers and mountaineering physicians as color commentary. Key Words: altitude; cor pulmonale; dilated; Everest; heart; pulmonary; ventricle (Baggish et al., 2014, Maggiorini et al., 2014). These include maintenance of adequate convective oxygen delivery to the working muscles and all tissues. As inspired oxygen pressure falls with increasing elevation and arterial blood oxygen content declines, both ventricles of the heart (as a combined system) must increase their output accordingly. This demand comes even as the oxygen supply to the cardiac muscle itself would be insufficient without considerable coronary vasodilation and greater oxygen extraction. Both ventricles must labor against increased vascular resistances and blood viscosity as the hemoglobin concentration rises in compensation for the reduced arterial partial pressure of oxygen (Pao2). Although the systemic vascular resistance, against which the left heart must work, is somewhat increased at high altitude, perhaps by as much as 20%–30% (Baggish et al, 2014), this pales against the 100%–500% increase in pulmonary vascular resistance the right ventricle must accommodate without loss of forward output (Swenson, 2013; Maggiorini et al., 2014). In fact, all work at high altitude suggests that the healthy normal left heart never fails to meet its demands (Ba¨rtsch and Gibbs, 2007; Reeves et al., 2007; Baggish et al., 2014). This is not the case for the right heart that is tasked with keeping pace with the left heart, but having to do so against a much greater percentage increase in its downstream resistance. The considerable variability among individuals of what is termed hypoxic pulmonary vasoconstriction (HPV) underlies the propensity for right heart strain and in the end, dilation and failure (cor pulmonale) in the unfortunate climbers recounted in this essay (Naieje, 2013, Swenson, 2013).

Introduction

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fter the 1933 British Expedition to Everest, leader Hugh Ruttledge looked back at the 1922 expedition and remarked, ‘‘Whether he had used oxygen or not, every member of both climbing parties, with the single exception of Somervell, was found to be suffering from a temporarily dilated heart’’ (Ruttledge,1934a, p 12). Surgeon T. Howard Somervell may have had difficulty examining himself and detecting heart dilatation on either the 1922 or 1924 expeditions when he was both a physician and mountaineer. This essay will feature high altitude pioneers and their many quotations about dilated, strained, or enlarged hearts occurring during long and high alpine expeditions. Most accounts deal with experiences in the Himalayas. This story is ultimately about the right ventricle (RV). Ironically, much of the understanding up until the mid-twentieth century implied failure of the left ventricle (LV) due to incomplete understanding of the unique stress of altitude and climbing on the right heart. Some physiology of the right side of the heart will be discussed as the story develops, but the ‘Words From On High’ style of the lead author (Lankford, 2009, 2014) will focus on mountaineers and mountaineering physicians to provide color commentary. A Brief Physiology of the Heart at High Altitude

The cardiovascular demands of high altitude climbing include stresses on both the right and left sides of the heart 1

Richmond, Virginia. Veterans Affairs Puget Sound Health Care System, Seattle, Washington.

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1894 Margherita Hut on Monte Rosa

The literary survey begins with Angelo Mosso, Professor of Pharmacology and Physiology at Turin. After his 1894 altitude studies at the Margherita Hut at 4560 m on Monte Rosa in the Italian Alps, Mosso’s book Fisiologia dell’ uomo sulle Alpi (1897) was translated into English, Life of Man on the High Alps (1898). Mosso paraphrases Englishman Thomas Clifford Albutt, the inventor of the convenient clinical thermometer: ‘‘In the summer of 1868, Albutt began a series of excursions in the Alps.He laid his hand on his heart.opened his shirt and ascertained by means of percussion that the right ventricle of the heart was much dilated’’ (Albutt, 1870, p. 29; Mosso, 1898, p. 68). Mosso also cites Roy and Adami (1888) who in their discussion of overstrained hearts include an altitude case they compare to the Albutt incident. Although no cardiac palpation was performed, they did note that Swiss guides recognized a difference between ordinary exertional fatigue and exertional fatigue at high altitude. The observation was astute, but the guides’ remedy of cognac was dubious. Mosso examined by percussion but also with the phonendoscope introduced in the same year by Italian physicians Eugenio Bazzi and Aurelio Bianchi. It was the first stethoscope to incorporate a diaphragm to augment auscultatory sounds. An ‘‘intercostal attachment’’ placed on the patient’s chest transmitted sounds to the main diaphragm device. Figures 1, 2, and 3 are from his Chapter 5 ‘‘Fatigue of the Heart’’ (Mosso, 1898, pp. 69, 75). Mosso’s team diagrammed left and right heart chamber locations under the chest wall before and after exercise, finding that, ‘‘The volume is augmented, the transverse diameter is greater and the apex is higher up.’’ He attributed changes in position to a ‘‘sinking’’ of the heart chambers caused by dilatation from incomplete emptying and that ‘‘fatigue of the heart is one of the most weighty factors in mountain-sickness’’ (Mosso,

FIG. 2. The Mosso team’s schematic diagram of the chest wall before and after exercise. 1898, pp. 68–76). He also observed what we call HAPE in a soldier, and the condition of the hut’s namesake, the visiting Queen of Italy whose, ‘‘cheeks had a slightly bluish colour’’ (Mosso, 1898, pp. 190, 319). 1894 Karakorum

A minor highlight also from 1894 was in the Karakorum Himalaya. Martin Conway made ‘‘sphygmograph tracings of our pulses and boiling-point observations for altitude. Several of the men were in a bad way’’ (1894, p. 77). A portable sphygmograph had been used by Mosso as well. Back in London, physiologist C.F. Roy could characterize Conway’s recordings and crudely estimate systemic arterial pressure, but not the more important pulmonary artery pressure. 1907 Trisul

Dr. Thomas Longstaff in 1907 led the ascent of 23,359 ft (7120 m) Trisul. The group continued on and, while still above 15,000 ft (4572 m), Arnold Mumm spent 5 days suffering from, ‘‘‘‘Mountain Lassitude’’.a phrase which belongs peculiarly to our party: it was invented by [Charles] Bruce. Longstaff, in his monograph on Mountain Sickness, has approved of and adopted it; it was left for me to illustrate its ravages.a profound reluctance to do anything today or tomorrow’’ (Mumm, 1909, p. 81). Heart size was not mentioned by any of them, but Longstaff is cited here because in his 1906 treatise, he ends a sentence with three words that would become well-used in the future, ‘‘’Mountain lassitude’ which few can escape at altitudes of over 19,000 ft— we refer to this height an altitude beyond which deterioration outstrips acclimatization’’ (1906, p. 55). 1921 and 1922 Everest

FIG. 1. Angelo Mosso’s team conducted studies in Turin and at 4560 m at the Margherita Hut in the Italian Alps in 1894. A phonendoscope was used to help make a diagram of a subject at rest.

The 1921 Everest Reconnaissance expedition book made no mention of heart size, but on the 1922 expedition that went higher, George Finch and EF Norton had abnormal heart exams, and George Mallory was considered worse off with

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FIG. 3. Mosso’s mountaineer-physician Dr. Vittorio Abelli drew this diagram showing heart dilation in two subjects after high altitude exercise. both dilation and a cardiac thrill (Longstaff, 1922, Holzel and Salkeld, 1986, p. 120). The durable Somervell observed that, ‘‘At the height of 26,000 feet, I took my pulse (which was 180) and my respirations (which were 50 to 55 to the minute).No doubt the heart must be young to stand this rate of beating for many hours; yet not too young, or it will easily become enlarged and permanently damaged.The chief point still remaining to be mentioned concerns the after-effects of the climbing of Everest.some were reported to have enlarged hearts, while in some the heart was normal’’ (1923, pp. 303–307). Somervell’s heart rate of 180 bpm was higher than the observed maximum of modern physiologists who state that for a given level of exercise, heart rate is greater at high altitude, although the rate that can be achieved at maximal exercise is reduced compared to sea level and parallels maximum oxygen consumption (Reeves et al., 1987). In 1960–1961 above the Silver Hut, scientific leader Dr. Griffith Pugh recorded mean maximal heart rates at 7420 m (24,343 ft) of 135 bpm (Pugh, 1962). The 1985 Operation Everest II hypobaric chamber study (Reeves et al., 1987) showed maximal heart rates of 118 bpm at 8848 m (29,028 ft) but some field studies have revealed higher heart rates. In two climbers at 8750 m (28,707 ft) on Everest, maximum heart rates were 142 and 144 bpm (Lundby and van Hall, 2001). All of these were acclimatized lowlanders, whereas the maximum heart rate of adapted high altitude dwellers may not be as limited (West et al., 2013, p. 273).

medical officer RWG Hingston, ‘‘examined the whole [surviving] party and reported that, without exception, all those who had been above Camp IV had their hearts dilated to a greater or lesser extent’’ (Norton, 1925, p. 144). Hingston’s exact words, in his section on ‘Physiological Difficulties,’ were, ‘‘The climbers were examined before we left the mountain. All of them showed signs of dilatation of the heart; in two it was decidedly marked. All were debilitated. All had wasted.’’ (1925, p. 259). Somervell and Hingston’s cardiac observations, including a 1–3 week recovery, would be referenced in the respiratory text of Joseph Barcroft. Knowing of dilated hearts in hypoxic cats in the lab, and recalling a cyanotic colleague exercising on a bicycle ergometer 4 years earlier in Peru, Barcroft wrote, ‘‘One would like to have had an X-ray shadow of his heart under these circumstances, for it is expected that the heart would undergo a degree of dilation at high altitudes’’ (1925, pp. 136–137). This yearning for scientific explanation ran opposite of most climbers. Mallory himself had said earlier that medical tests, ‘‘are of no value in determining where precisely on that other hill of unrivalled altitude persevering man will be brought to a standstill.the scientists may explain your feelings, but when it comes to prophecy they have less right to be heard than a high-climbing mountaineer’’ (1922, p. 425). Dr. C Raymond Greene on a different mountain would say it in a different way about the exacting demands of study: ‘‘some have shown signs of heart trouble.[but] no mountaineer has yet to be found who will on his return submit to an autopsy in the cause of science’’ (1932, pp. 40–43).

1924 Everest

The 1924 expedition was known for being the one where George Mallory and Sandy Irvine were lost. We learn from leader EF Teddy Norton in The Fight for Everest 1924 that

1931 Kamet

In 1931, Kamet 25,446 ft (7756 m) became the highest summit yet attained. F.S. (Frank) Smythe was a mountaineer

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and a prodigious and witty author-lecturer. Smythe observed the cardiopulmonary effects of hypoxemia, ‘‘Even the effort of rising to our feet served like the touch of a foot on the sensitive throttle of a powerful racing car, to set the machinery of heart and lungs pounding furiously.’’ (1932, p. 197) He would declare it another way on Everest, ‘‘My legs were unusually weak and my heart was still hammering unpleasantly against my ribs’’ (Smythe, 1937, p. 588). Greene was part of the 1931 team that climbed Kamet. In 1933 he was the senior doctor and mountaineer on the fourth British Everest expedition. In 1953 when Everest was finally climbed, it was Greene who made the announcement on the BBC. Only a little is mentioned about hearts on Kamet in 1931, but his medical approach to acclimatization tried chemistry. Greene comments that, ‘‘It had been suggested by Haldane that the process of overcoming the ‘‘alkalosis’’ of high altitudes might be accelerated by the administration of ammonium chloride’’ (1932, p. 340). The recommendation had come from John Scott Haldane, the Scottish physiologist respected for his important studies of oxyhemoglobin dissociation, blood gases, control of respiration, and conditions such as carbon monoxide poisoning and caisson’s disease. Unfortunately, his 1911 Pike’s Peak, Colorado study erroneously theorized lung secretion of oxygen into capillary blood (rather than passive diffusion alone) at high altitude (Douglas et al., 1913). Greene treated himself with ammonium chloride the entire time he was above 15,000 ft (4572 m) on the Kamet journey but admitted that, ‘‘A single experiment of this sort cannot be regarded as of any scientific importance. Nor was it obvious that I acclimatized any better than any other member of the expedition’’ (1932, p. 446). Smythe reveals that at least one other climber was a test guinea pig, ‘‘Recently, Greene had experimented with ammonium chloride, and administered this to himself and Beauman.Whether or not the experiment had the desired effect of hastening Beauman’s acclimatisation must remain non-proven’’ (1932, p. 180). Ammonium chloride has side effects and later was found to be not efficacious and even a handicap to acclimatization (Barron, 1937). Smythe returns to the main subject of this essay with this heart comment while descending from Base Camp for, ‘‘rest at a reasonable altitude in order to recoup strength and allow enlarged hearts to return to their normal size’’ (1932, pp. 236–237). 1933 Everest

The 1933 Everest expedition once again did not reach the top. Before telling that story and more about climbers’ hearts, we will describe another medical event, a cardiopulmonary arrest. After crossing a Tibetan pass of about 16,000 ft (4876 m), ‘‘Lopsang Tsering fell off his pony and broke his collarbone; the anaesthetic administered by Greene stopped his heart, and only vigorous resuscitation, aided by coramine, saved his life’’ (Ruttledge, 1934a, p. 95). Expedition doctor Greene had administered chloroform by the open-drop method, a drug and method known to be potentially lethal ever since the ‘father of epidemiology’ John Snow’s report on chloroform fatalities (Snow, 1849). An anesthesia history article summarizes the problems, ‘‘The patient’s subsequent apparent cardiopulmonary arrest has long been attributed to the effects of altitude on anaesthetic delivery.problems may have arisen from.chloroform va-

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porisation in a cold environment, Greene’s concern about potential depression of ventilation and the contemporary lack of a precise approach to assessing depth of anaesthesia’’ (Firth and Pattinson, 2008). The rescue drug, Coramine (nikethamide or nicotinic acid diethylamide), was often used as a respiratory stimulant countermeasure against tranquilizer overdoses before the advent of endotracheal intubation (Reynolds, 1993, p. 1229). The most famous patient was Adolf Hitler. His personal physician injected the Fuhrer with Coramine as part of a polypharmaceutical tonic and also when Hitler was unduly sedated with barbiturates (Doyle, 2005). Through the years, it has been used by athletes, including mountain climbers, for example, on the Eiger (Olsen, 1962) and even as recently as 2013 when a pro tennis player was bounced out after testing positive for the stimulant (Bruce, 2013). Nikethamide is a banned substance, listed by the World Anti-Doping Agency as prohibited in competition–category S6–Stimulants (WADA, 2014). The 1933 party reached the Rongbuk monastery in Tibet and turned south 4 miles to Base Camp at roughly 16,800 ft (5120 m) (Ruttledge, 1934a, p. 237). Above that, the East Rongbuk glacier was followed to the North Col of Everest where higher and higher camps had to be stocked. Smythe notes that ‘‘The slightest exertion accelerated my heart and I wondered dismally whether I had strained it.beyond all hope of repair. Anyone who makes a severe physical effort over 22,000 feet has to pay for it afterwards‘‘ (1937, pp. 588– 589). Indeed, life was hard at those altitudes, but Raymond Greene who was a brother of novelist Graham Greene, perhaps carried some raconteur genes to high altitude. Smythe: ‘‘We were a merry party that evening in the arctic tent, and Raymond.once again entertained us with some of his stories, which not even an altitude of 22,000 feet could dull in the telling’’ (1937, p. 585). It was not always so jovial. Greene jokes darkly, ‘‘I recalled a toilsome trudge across a Himalayan glacier and the knowledge that with no taxi to help me I must reach my tent or die’’ (1974, p. 151). Oxygen was half-tried at the 23,031 ft (7020 m) North Col by Smythe who was descending after his summit attempt. He stopped it because of a dry throat. Ruttledge speculated that ‘‘A climber will receive little or no benefit from the use of oxygen at an altitude to which he has acclimatised himself’’ (1934a, p. 283). At that time, the height limit of long-term versus short-term acclimatization was not fully understood. Early oxygen systems were such a burden that climbing advantage was debated and the other benefits to warmth, endurance, sleep, and mentation were only partially appreciated. Greene also tried oxygen, but from another source. He was expected to go high but at 25,700 ft (7833 m) Camp V, he had, ‘‘staggered in.exhausted.One day’s acclimatization at Camp IV had not been enough, and he had strained his heart’’ (Ruttledge, 1934a, p. 148). This happened despite finding an old but still-pressurized 1922 oxygen tank, breathing some of it for ‘‘half a minute’’ with ‘‘remarkable’’ results, and then continuing on without it. Oxygen can rapidly reduce pulmonary hypertension within 5–10 minutes but in ‘‘half a minute’’ it is more likely he felt relief from cerebral hypoxia or other reasons. Ever the scientist, Greene obtained alveolar air samples at Camp V, ‘‘but was in no condition to stay there’’ (Ruttledge, 1934a, p. 149). On the way down to Camp III, he was described as, ‘‘a really sick man, with heart trouble.’’ (Ruttledge, 1934a, p. 158).

DILATED HEARTS AT HIGH ALTITUDE 1933 Everest Summit Attempts

The first 1933 attempt by Lawrence Wager and Percy Wyn-Harris was famous for finding the ice-axe belonging to Irvine who disappeared with Mallory in 1924. On their descent, Second Medical Officer William McLean had examined them and ‘‘speedily determined that both men had dilated hearts and would be out of action for some time’’ (Ruttledge, 1934a, p. 180). The second 1933 attempt was by Eric Shipton and Smythe. The former turned back, leaving Smythe alone. Like the first attempt, he also reached the vicinity of Norton’s 1924 ascent to 28,120 ft (8570 m) without supplemental oxygen, a record not broken until 1978 when Reinhold Messner and Peter Habeler reached the summit from the Nepal side. On the way back down, Smythe had his famous hypoxic hallucinations of pulsating kites and sharing a mint with an imaginary companion. With his usual wit, he declares that ‘‘Save for my legs, which had an unpleasant habit of giving way under me every few yards, I felt quite fit’’ (Smythe, 1934, p. 216). After the second attempt, Ruttledge details several heart observations, ‘‘Greene now constituted himself a Medical Board.Smythe was passed with credit. Except for some loss of weight, he appeared to be fit as ever, his heart quite unaffected by high ascent.Wyn Harris’s heart had regained normal proportions and, so far as could be seen, he could go high again.Wager, whose heart required a longer rest, would have to remain for the present at the Base Camp’’ (Ruttledge, 1934a, p. 226). A third attempt was aborted because of snow conditions and altitude deterioration of some of the party. Greene himself, for example, was ‘‘far from well. The week’s rest, effective as it seemed at Base Camp, was insufficient’’ (Ruttledge, 1934, p. 231). As for the others who were in better shape, Ruttledge could see that they, too, ‘‘were not so fresh as they had been’’ (1934a, p. 232). Not all of this was attributed to dilated hearts alone but altitude deterioration. Ruttledge acknowledges that ‘‘long residence at Camp IV and above allowed deterioration to set in’’ (1934a, p. 279) and that the, ‘‘number of climbers who had shown themselves capable of going high was small. Of them, too, some had dilated hearts; while everyone had obviously lost weight and condition during the past few weeks’’ (Ruttledge. 1934b). Greene saw the deterioration in himself, exclaiming, ‘‘I took off my clothes for the first time in six weeks and had my first bath. I was horrified by the wasted muscles’’ (1974, p. 164). The decision to leave was celebrated, the only problem being that champagne, ‘‘is very difficult to manage at a height of 16,800 ft. Atmospheric pressure being so low, a large proportion of the wine follows the cork up to the ceiling’’ (Ruttledge, 1934, p. 237). 1938 Everest

After the 1938 Everest attempt, leader HW Bill Tilman was on a 47-mile day trip over a 14,000ft (4267 m) pass in Sikkim. Tilman famously eschewed science on the mountains, but made the point that, ‘‘though men coming off Mount Everest are usually in very poor condition, often with dilated hearts, recovery does not take long’’ (1946, p. 278). Expedition physician Charles Warren would have performed any examination. 1943 Mountain Warfare Training Centre

In 1943 British physiologist and physician Griffith Pugh evaluated military ski trainees at ‘The Cedars’ Mountain

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Warfare Training Centre at a moderate altitude of 6890 ft (2100 m) in Lebanon. The tallest peak climbed was Cornet es Saouda 10,095 ft (3077 m). Pugh found that after only a few days of hard ski-mountaineering two men had ‘‘dilated hearts’’ on physical examination, the total rising to 10 of 33 after 2 weeks (1943). Pugh went on to higher altitude studies, including Cho Oyu in 1952, Everest in 1953, and his most recognized project in the next decade. 1960–1961 Himalayan Scientific and Mountaineering Expedition

The Silver Hut and Makalu expeditions of 1960–1961 led by Griffith Pugh and Edmund Hillary accomplished much science but suffered serious high altitude medical events on the Makalu attempt. Hillary had a stroke at 19,500 ft (5943 m). James Milledge forsook the mountain to care for Hillary who recovered at lower altitudes. Others continued the assault on Makalu but at 27,400 ft (8351 m) were forced to turn back with Peter Mulgrew coughing up blood, Michael Ward confused from either simple hypoxia or HACE, Tom Nevison with HAPE, and Sherpa Angtemba with an orthopedic injury. On their descent, a team of Sherpas came up led by John West. Using oxygen, the Australian physiologist and physician ‘‘came amongst us like a whirlwind—a wonderful breath of fresh air. Only then did I realize how badly we had all deteriorated.Mulgrew’s colour was dreadful, his eyes were sunken and lifeless, and his breath came in uneven shudders. His hands and feet were a horrible blotchy purple and intermittently he coughed blood’’ (Harrison, 1961). After a morphine injection, the now unconscious Mulgrew was evacuated on a stretcher improvised from tent poles. Mulgrew, Ward, and Angtemba were flown to a Kathmandu hospital where the severely frostbitten Mulgrew was diagnosed with pulmonary thrombosis and infarct (Mulgrew, 1964, p. 141). Ward had heart involvement because ‘‘An Xray of Ward’s chest at Kathmandu, taken within twenty-four hours of returning by helicopter, showed an enlarged heart. Further X-rays at the London Hospital showed a gradual diminution in size of his heart until it became normal in size after three months’’ (Mulgrew, 1964, p. 192). Pugh’s account states the same saga in succinct, sterile, scientific speech, ‘‘Changes characteristic of right ventricular hypertrophy were present in the V leads, and a chest x-ray examination of a climber flown back to Katmandu from Makalu showed enlargement of pulmonary artery and increased convexity of the right border of the heart. Six weeks later the radiological findings were normal. These findings taken together are evidence of right ventricular hypertrophy secondary to pulmonary hypertension’’ (Pugh, 1962). This may have been the earliest accurate description of the true nature of the much-described abnormal hearts in the mountaineering literature. Physiology—Early Medical Thoughts

Early medical thoughts about high altitude were limited because of the knowledge of the day. Cardiology at high altitude was centered on failure to acclimatize, high altitude deterioration, and degeneration of the heart generally meaning the LV (Naeiji, 2013; West, 2013, p. 102). The following two noncardiac examples exemplify the degree of diagnostic difficulty or frank misunderstanding.

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The first example is from Hingston on the 1924 expedition writing about Cheyne-Stokes or periodic breathing of high altitude, ‘‘It was most pronounced in one member when suffering from fever at 15,000 feet, and still more so in a Gurka when dying of cerebral haemorrhage at 18,000 feet’’ (1925, p, 244). Instead, the ‘‘cerebral haemorrhage’’ may have been an altitude headache with stroke-like or coma presentation of high altitude cerebral edema (HACE). The second example is also from Hingston, critical of a hematology misconception, ‘‘Professor [AE] Boycott has made a heroic suggestion. He points out that the capacity to increase red corpuscles can be increased as a result of practice.Professor Boycott suggests that the best preparation for the next expedition would be to have the party repeatedly bled’’ (1925, p. 248). Nowadays a pre-trip round of erythropoietin or nights in a hypobaric tent would make more sense. Respiratory symptoms in hypoxemic mountaineers were perhaps easier to fathom. From the 1924 expedition, Noel Odell exclaims that ‘‘The hard breathing at these altitudes would surprise even a long-distance runner’’ (1925, p. 137). In 1978, during the first ascent of Everest with Habeler and without supplemental oxygen, a panting Messner utters ‘‘I am nothing but a single narrow gasping lung’’ (1979, p. 180). These hyperventilation quotations from climbers are clearly about a different physiological situation than the hypoventilation problem of Chronic Mountain Sickness (CMS) or Monge’s disease. That condition is characterized by runaway polycythemia, cyanosis, somnolence, and fatigue. The right ventricle (RV) is impacted in both of these situations at high altitude, however, Europeans may not have known in a timely fashion about Monge’s 1925 report and his book published in Peru (1928). Another obscure but more appropriate clue was from the veterinary literature in 1915. In Colorado, George Glover and Isaac Newsom described brisket disease (1915), the bovine equivalent of human high altitude RV failure. Examination of the Heart

Although physicians and stethoscopes for auscultation were taken on some expeditions, there was no radiology or echocardiography, so palpation and percussion was performed (Naeije, 2013). Finger-on-finger percussion had been described in 1828 by Pierre Piorry, an improvement on the earlier one-handed thumping method. The non-striking finger (pleximeter) is placed over the body part, in this case the heart. The sound from the tapping finger (plexor) may be resonant, tympanic, or dull, and thereby size estimated. Manual examination also includes palpation of thrills and the point of maximal impact for the LV is normally in the midclavicular line at the fifth intercostal space. The RV is located more antero-medially. With RV dilatation or hypertrophy, findings more likely at high altitude, the RV systolic impulse may be felt parasternally and at a higher intercostal space. Unfortunately, these details were not given in any of the book quotations of the early mountaineering authors and physicians mentioned here, except for Mosso at the Margherita hut in 1894. How and when the examination methods of Mosso, and others, were disseminated and came into wider clinical usage by mountaineer physicians and nonphysicians is unknown. How many of their observations were acute RV dilatation (with faster resolution on descent), or RV hypertrophy during longer stays, is unknown. These longer-stay

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cases, such as Ward on Makalu in 1961, with Pugh describing hypertrophy, may have been what happened later to Indian soldiers stationed at high altitude borders for months (Anand et al., 1990). Moving forward to 1993, percussion and palpation were compared to computed tomography, at least for the LV, and revealed moderate reproducibility with limitations (Heckerling, 1993). Modern diagnostic technologies have further reduced the reliance on examination skills (Federowski, 2000). Right Ventricular Dilatation, Hypertrophy, Failure, and High Altitude Pulmonary Edema

The pulmonary circulation is normally a low-pressure, high-capacitance system. The pulmonary vasculature can accommodate large increases in blood flow, as during routine exercise or sudden occlusion of some of the pulmonary arteries, with little or no increase in pressure. In most normal humans, the RV may be unable to generate a peak systolic pressure > 40–50 mmHg acutely, a level that ultimately develops in high altitude climbers over a period of days to weeks. One of the factors is the crescent-shaped geometry of the RV that makes the chamber poorly tolerant of acute afterload elevations. Modest increases in pulmonary vascular tone can cause the thin-walled distensible RV to fail. Acute cor pulmonale usually results in RV dilatation, whereas chronic cor pulmonale usually results in RV hypertrophy and pressures that can be even higher (Matthews and McLaughlin, 2008). The exception to the limited rise in pulmonary artery pressure with hypoxia in most persons is the much stronger acute response of individuals with susceptibility to high altitude pulmonary edema (Ba¨rtsch and Swenson, 2013). High altitude initiates hypoxic pulmonary vasoconstriction (HPV) resulting in pulmonary hypertension and afterload on the RV (Swenson, 2013). This may be followed by a cascade of endothelial, cellular, edematous, and other changes to produce high altitude pulmonary edema (HAPE). Physical findings of HAPE are described in a general medicine emergency manual (Carstairs, 2012) as including ‘‘signs of pulmonary hypertension, such as a prominent P2 and right ventricular heave.’’ The high altitude medical text of West et al. (2013, p. 313) states that cardiac signs in HAPE, depending on severity, include ‘‘right ventricular heave and accentuated pulmonary second sound in about half the patients. Signs of right ventricular failure are not prominent.’’ In extreme cases of acute RV failure, such as large pulmonary emboli, cardiac findings may include ‘‘RV heave, increased pulmonary component of the second heart sound, a rightsided S3, a tricuspid regurgitation murmur, jugular venous distention, and peripheral cyanosis and edema’’ (Matthews and McLaughlin, 2008). Right Ventricle and Pulmonary Artery Structural Remodeling

Muscularization of the pulmonary branches, pulmonary artery pressure, and RV effects vary. For example, there are differences in age, HPV sensitivity, and lowlanders versus high altitude Andean dwellers versus adapted-over-morecenturies Tibetans (Swenson, 2013). This has implications for stress on the RV at high altitude acutely, as in climbers, or chronically, as in dwellers.

DILATED HEARTS AT HIGH ALTITUDE

Ba¨rtsch and Gibbs (2007) and Naeije (2013) reviewed studies of high altitude pulmonary hypertension (HAPH) and right heart failure syndromes described under various names, including brisket disease in cattle brought to high-altitude pastures, CMS or Monge’s disease in South America, Han Chinese immigrants and/or infants brought to Tibet (Wu and Liu, 1955; Sui et al., 1988), occasional RV failure in previously healthy travelers, and subacute mountain sickness (SAMS) with rapidly-evolving RV failure in Indian soldiers posted for months at high-altitude borders (Anand et al., 1990). The term SAMS is misleading because it is not related to acute mountain sickness (AMS) and the term ‘right heart failure of high altitude’ had been suggested. Many of the lengthy expeditions quoted here may have had climbers affected like these Indian soldiers. At high altitudes, heart failure is predominantly right sided, explained by HPV, pulmonary hypertension, and remodeling as a cause of increased RV afterload with a contribution of negative inotropic effects of hypoxia and hypoxia-induced neuroendocrine activation. To what extent, if any, the skeletal muscle wasting of prolonged high altitude sojourning affects cardiac muscle and leads to cardiac dilation remains only minimally explored, but recent evidence suggest that the heart is not spared (Wagner, 2010; Holloway et al., 2011). Rapid Right Ventricular Failure at High Altitudes

While the RV usually responds well to the demands of high altitude (Naeije, 2013), RV failure can be rapid in some individuals. A sample case report includes a mountaineer in 2007 who within the first 24 h after arriving at 3700 m in Bolivia developed dyspnea and cardiac signs of pulmonary hypertension (Huez et al., 2007). Echocardiography showed an elevated pulmonary artery mean pressure of 80 mm Hg and RV dilatation. All findings resolved with descent. Similar clinical rapidity can occur in cattle, a species known to be exquisitely altitude-sensitive ever since Glover’s 1915 account. The altitude involved can be strikingly low, such as in heifers taken from 275 m in Wisconsin to only 1600 m in Colorado. Progressive right-sided heart failure or brisket disease ranked second only to pneumonia in the Rockies as a cause of death in a 5-year veterinary study (Malherbe et al., 2012). Clinical rapidity in development and then resolution can also be seen in runners. Echocardiography was performed before and after the 1994 Hardrock ultramarathon at altitudes of 2350–4300 m in Colorado. Pulmonary hypertension, right ventricular dilatation, and hypokinesia developed in a third of studied participants, and reversed in one day (Davila-Roman et al., 1997). 1995—A Famous Climber and the Right Ventricle

John Hunt, leader of the 1953 British Everest Expedition, presented much later at age 85 with dominant RV failure in the absence of either CMS or overt LV failure. In 1936 he had an unspecified murmur detected at sea level, but in 1995 developed cardiac enlargement and auscultatory signs of aortic stenosis and tricuspid regurgitation. Echocardiography confirmed moderate aortic stenosis, LV hypertrophy, RV dilatation, severe tricuspid regurgitation, right atrial hypertrophy, and pulmonary artery pressures that were only upper normal (Marchbank et al., 1998). Not mentioned by the authors was that the lower-than-expected pulmonary artery

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pressures might have represented the dynamics of a failing RV. Because a right atrial biopsy showed histiologic signs of chronic pulmonary hypertension, they leaped to the conclusion that his findings were caused by intermittent but prolonged exposures to high altitude, although any chronic LV dysfunction or left-sided valvular disease leads to secondary pulmonary hypertension. There are species and human individual, ancestral, and HAPE-prone pulmonary vascular responses to high altitude. The authors’ speculation about Hunt, if true, would indicate that his pulmonary vasculature was unusually sensitive (such as has been documented for those who are susceptible to HAPE), that the pulmonary hypertension had reversed as it should on descent to sea level where he spent far more years of his life, but that the intermittent exposures at extreme altitude had somehow irreversibly changed the right side of his heart. The Future

Naeije states that RV failure even in pre-existing pulmonary hypertension patients is rare unless they have pronounced vascular hyper-reactivity (2013). Applicable to possible forthcoming studies, he remarks that ‘‘whether preconditioning of the right ventricle occurs in physically active mountaineers as in highly trained endurance athletes would be interesting to investigate.’’ Conclusion

In their own ways and time, Mosso, Monge, and Pugh had it right. Modern medicine has a better but still evolving understanding of the cardiopulmonary dynamics at high altitude, particularly of the right side and the lesser circulation. To us, the misery described in the writings of the high altitude pioneers helps to tell the story in an equally unique and more evocative manner, both in terms of the mountain literature and illustration of some of the high altitude illnesses and physiology. Acknowledgments

Special thanks to mountaineering historian George Rodway for alerting to us the Mosso source and his seminal cardiac observations, which, like much of his work at high altitude, were correct and groundbreaking. Author Disclosure Statement

Neither author has any conflict, funding, or affiliation to report related to this essay. References

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Address correspondence to: Harvey V. Lankford, MD, FACE 8001 Riverside Drive Richmond, VA 23225 E-mail: [email protected] Received April 28, 2014; accepted in final form July 12, 2014.