Why isn’t my patient with congestive heart failure or end-stage liver disease losing weight despite being on diuretic therapy? Is the diuretic dose too low, or is the salt intake too high?

When a patient with congestive heart failure (CHF) or end-stage liver disease (ESLD) doesn’t respond as expected to diuretic therapy, measurement of urinary sodium (Na) can be helpful.

In low effective arterial blood volume states (eg, CHF and ESLD) aldosterone secretion is high, resulting in high urine potassium (K) and low urine Na concentrations. However, in the presence of diuretics, urinary Na excretion should rise.

Patients undergoing active diuresis are often restricted to a 2 g (88 mEq) Na intake/day, with ~10 mEq excreted via non-urinary sources (primarily stool), and ~ 78 mEq excreted in the urine to “break even” — that is, to maintain the same weight.

Although historically measured 1, a 24-hour urine Na and K collection is tedious, making spot urine Na/K ratio more attractive as a potential proxy.  Approximately 90% of patients who achieve a urinary Na/K ratio ≥1 will have a urinary Na excretion ≥78 mEq/day — that is to say, they are sensitive to the diuretic and will have a stable or decreasing weight at the current dose. 2,3

Urine Na/K may be interpreted as follows:

  • ≥1 and losing weight suggests effective diuretic dose, adherent to low Na diet
  • ≥1 and rising weight suggests effective diuretic dose, non-adherent to low Na diet
  • <1 and rising weight suggests ineffective diuretic dose

The “ideal” Na/K ratio as relates to responsiveness to diuretics has ranged from 1.0 to 2.5.4 In acutely decompensated heart failure patients on spironolactone, a K-sparing diuretic, Na/K ratio >2 at day 3 of hospitalization may be associated with improved outcome at 180 days. 5

Remember also that if the patient’s clinical syndrome is not correlating well with the ratio, it’s always a good idea to proceed to a 24-hour urine collection.



  1. Runyon B. Refractory Ascites. Semin Liver Dis. Semin Liver Dis. 1993 Nov;13(4):343-51. https://www.ncbi.nlm.nih.gov/pubmed/8303315
  2. Stiehm AJ, Mendler MH, Runyon BA. Detection of diuretic-resistance or diuretic-sensitivity by spot urine Na/K ratios in 729 specimens from cirrhotics with ascites: approximately 90 percent accuracy as compared to 24-hr urine Na excretion (abstract). Hepatology 2002; 36: 222A.
  3. da Silva OM, Thiele GB, Fayad L. et al. Comparative study of spot urine Na/K ratio and 24-hour urine sodium in natriuresis evaluation of cirrhotic patients with ascites. GE J Port Gastroenterol 2014;21:15-20 https://pdfs.semanticscholar.org/4dc3/4d18d202c6fa2b30a1f6563baab80d877921.pdf
  4. El-Bokl M, Senousy, B, El-Karmouty K, Mohammed I, Mohammed S, Shabana S, Shelby H. Spot urinary sodium for assessing dietary sodium restriction in cirrhotic ascites. World J Gastroenterol 2009; 15:3631. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721236/
  5. Ferreira JP, Girerd N, Medeiros PB, et al. Spot urine sodium excretion as prognostic marker in acutely decompensated heart failure: the spironolactone effect. Clin Res Cardiol 2016;105:489-507. https://www.ncbi.nlm.nih.gov/pubmed/26615605


Contributed by Alyssa Castillo, MD, with valuable input from Sawalla Guseh, MD, both from Mass General Hospital, Boston, MA.

Why isn’t my patient with congestive heart failure or end-stage liver disease losing weight despite being on diuretic therapy? Is the diuretic dose too low, or is the salt intake too high?

Should my patient with compensated heart failure be placed on a sodium-restricted diet?

Although sodium restriction is routinely recommended for patients with heart failure (HF), the data is often conflicting with a number of studies suggesting that it may be harmful in some HF patient. 

Two randomized trials (by the same group) involving patients with compensated HF recently discharged from the hospital reported that “less restricted” sodium diet (2.8 gm/d) along with fluid restriction (1 liter/d) and high-dose furosemide (at least 125-250 mg furosemide bid) was associated with less rates of readmissions and improved levels of brain natriuretic peptide, aldosterone and plasma renin activity when compared to patients on more restricted sodium diet (1.8 gm/d).1,2

Analysis of data from the multihospital HF Adherence and Retention Trial enrolling New York Heart Association functional class II/III HF patients found that sodium restriction (<2.5 gm/d) was associated with significantly higher risk of death or HF hospitalization but only in patients not on an angiotension converting enzyme inhibitor or angiotensin receptor blocker.3

In normal subjects who are not sodium deprived, excess sodium intake has been shown to cause expansion of intravascular volume without increasing total body water.4 Thus, sodium restriction combined with diuretics may reduce intravascular volume and renal perfusion, further stimulating the renin-angiotensin-aldosterone system and fluid retention.5

Now that’s interesting! Did you know that the 2013 American College of Cardiology Foundation/American Heart Association guidelines downgraded the recommendation for sodium restriction to Class IIa (reasonable) with Level of Evidence:C? 6



  1. Paterna S, Gaspare P, Fasullo S, et al. Normal-sodium diet compared with low-sodium diet in compensated congestive heart failure: is sodium an old enemy or a new friend? Clin Sci 2008;114:221-230. https://www.ncbi.nlm.nih.gov/pubmed/17688420
  2. Paterna S, Parrinello G, Cannizzaro S, et al. Medium term effects of different dosage of diuretic, sodium, and fluid administration on neurohormonal and clinical outcome in patients with recently compensated heart failure. Am J Cardiol 2009;103:93-102. https://www.ncbi.nlm.nih.gov/pubmed/19101237
  3. Doukky R, Avery E, Mangla A, et al.Impact of dietary sodium restriction on heart failure outcomes. J Am Coll Cariol HF 2016;4:24-35. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705447/
  4. Heer M, Baisch F, Kropp J et al. High dietary sodium chloride consumption may not induce body fluid retention in humans. Am J Physiol Renal Physiol 2000;278:F585-F595. https://www.ncbi.nlm.nih.gov/pubmed/10751219
  5. Rothberg MB, Sivalingam SK. The new heart failure diet: less salt restriction, more micronutrients. J Gen Intern Med 25;1136-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955483/
  6. Yancy CW, Jessup M, Bozkurt B, et al. 2013 CCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:e147-239. https://www.ncbi.nlm.nih.gov/pubmed/23741058
Should my patient with compensated heart failure be placed on a sodium-restricted diet?

My patient with COPD has new clubbing of his finger tips. What is the mechanism of clubbing?

The mechanism behind digital clubbing has yet to be fully elucidated, with hypotheses ranging from a circulating vasodilator, tissue hypoxia, a neurocirculatory reflex, and genetic factors. 1 Although hypoxemia is often cited as a cause of clubbing, it is often absent in the presence of clubbing and many patients with hypoxemia do not have clubbing.

A potentially unifying pathophysiologic mechanism of clubbing revolves around platelet clustering and associated growth factor release. 2.3 Platelet clumps/megakaryocytes—either because of circumvention of the lung capillary network (eg, in intracardiac shunts or lung cancer) or increased production (eg, in left-sided endocarditis or chronic inflammatory conditions)—may wedge in the fine vasculature of distal fingertips or toes and cause release of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF).

Together, PDGF and VEGF promote neovascularization, increase vessel dilation and permeability, and modify connective tissue to create the distinct club-like appearance. Local hypoxic condition from reduced capillary perfusion is thought to further stimulate the release of these growth factors.

Potential causes of clubbing in our patient include lung cancer, interstitial lung disease, bronchiectasis, core pulmonale and secondary polycythemia, among many others. 1

Fun Fact: Did you know that clubbing, also known as “Hippocratic finger”, was first described by Hippocrates in a patient with chronic empyema (don’t ask how chronic empyema was diagnosed in 400 BC!)?1



  1. McPhee SJ. Clubbing. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths;1990. Chapter 44. Available from https://www.ncbi.nlm.nih.gov/books/NBK366/
  2. Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet 1987;2:1434-4. https://www.ncbi.nlm.nih.gov/pubmed/2891996/ 
  3. Atkinson S, Fox SB. Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) play a central role in the pathogenesis of digital clubbing. J Pathol 2004;203:721-8. https://www.ncbi.nlm.nih.gov/pubmed/15141388


Contributed by George Bugarinovic, Medical Student, Harvard Medical School

My patient with COPD has new clubbing of his finger tips. What is the mechanism of clubbing?

My patient is asking about the benefits of smoking cessation. How soon should she realize the health benefits of quitting her habit?

She should realize the health benefits of smoking cessation (SC) almost immediately! As the effect of nicotine wears off, just 15-20 minutes after her last cigarette, her heart rate and blood pressure should begin to fall.1,2Other health benefits, some within a year others longer, soon follow. 3,4 Between 2-12 weeks after SC, your patient may notice an improvement in her breathing and pulmonary function tests.

Between 1-9 months, the cilia in the lungs should begin to regenerate and regain normal function, allowing her to adequately clear mucus and bacteria with a decrease in cough and shortness of breath.

At 1 year, the risk of cardiovascular disease (eg, myocardial infarction, stroke) falls by one-half.

At 5 years, the risk of mouth, throat, esophagus, and bladder cancer also drops by one-half.

It takes 10 years for the risk of lung cancer to drop by one-half, and 15 years for it to approach that of non-smokers asymptotically. 4Fun fact: Did you know that in hypertensive patients who smoke, the blood pressure lowering effect of beta-blockers may be partly abolished by tobacco smoking,  whereas alpha-blockers may maintain their antihypertensive effects? 5References

  1. Omvik P. How smoking affects blood pressure. Blood Press. 1996;5:71–77. https://www.ncbi.nlm.nih.gov/pubmed/9162447
  2. Mahmud A, Feely J. Effect of smoking on arterial stiffness and pulse pressure amplification. Hypertension. 2003;41(1):183-187. https://www.ncbi.nlm.nih.gov/pubmed/12511550
  3. US Surgeon General’s Report, 1990, pp. 193, 194, 196, 285, 323
  4. US Surgeon General’s Report, 2010 and World Health Organization. Tobacco Control: Reversal of Risk After Quitting Smoking. IARC Handbooks of Cancer Prevention, Vol. 11. 2007, p. 341.
  5. Trap-Jensen. Effects of smoking on the heart and peripheral circulation. Am Heart J 1988;115:263-7.   https://www.ncbi.nlm.nih.gov/pubmed/3276115

Contributed by Felicia Hsu, Medical Student, Harvard Medical School

My patient is asking about the benefits of smoking cessation. How soon should she realize the health benefits of quitting her habit?

How does hyperventilation cause coronary vasospasm?

Hyperventilation may be an important cause of coronary vasospasm and chest pain. 1 The mechanism likely revolves around the competition between the effects of hydrogen and calcium ions on the smooth muscle of coronary arteries. 2

Respiratory alkalosis induced by hyperventilation causes a reduction of hydrogen ions which, under physiologic conditions, compete with calcium ion, an important trigger for arterial smooth muscle contraction. Lower hydrogen ion concentrations tips the balance in favor of calcium’s effects on transmembrane channels and myofibrillar ATP-ase of the smooth muscle and causes vasoconstriction.2

In fact, hyperventilation has been used to reproduce coronary spasm during angiography in patients with non-obstructive coronary artery disease and angina symptoms.The efficacy of hyperventilation in inducing an alkalotic state during this test is verified by obtaining an arterial blood gas after 6-minutes of hyperventilation.  A basic Tris-buffer to enhance alkalotic provocation was also used in earlier studies. 2

In addition to producing spasm and angina, hyperventilation-induced alkalosis has been associated with frank transmural myocardial infarction and ischemia-related arrhythmias such as ventricular tachycardia. 2,4,5

So in the appropriate context, hyperventilation may not be so benign!


  1. Freeman LJ, Nixon PGF. Chest pain and the hyperventilation syndrome-some aetiologic considerations. Postgrad Med J 1985;61:957-61. http://pmj.bmj.com/content/postgradmedj/61/721/957.full.pdf
  2. Yasue HM, Nagao S, Omote A, et al. Coronary arterial spasm and Prinzmetal’s variant form of angina induced by hyperventilation and Tris-buffer infusion. Circulation 1978;58:56-62. https://www.ncbi.nlm.nih.gov/pubmed/25720
  3. Zaya M, Mehta PK, Merz NB, etal. Provocative testing for coronary reactivity and spasm. J Am Coll Cardiol 2014; 63:103-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914306/pdf/nihms549572.pdf
  4. Magarian GJ, Jones S, Calverley T. Hyperventilation testing for coronary vasospasm: induction of spontaneous ventricular tachycardia in association with transmural ischemia without obstructive coronary disease. 1990; 120:1447-49. http://journal.chestnet.org/article/S0012-3692(16)52837-2/pdf
  5. Chelmowski MK, Keelan MH. Hyperventilation and myocardial infarction. Chest 1988;93:1095-96. https://www.ncbi.nlm.nih.gov/pubmed/3359829



Contributed by Ramya Chitra Mosarla, Medical Student, Harvard Medical School

How does hyperventilation cause coronary vasospasm?

My patient with acute exacerbation of heart failure and pulmonary edema also has pneumonia. How often do heart failure and pneumonia coexist?

More often than you might think! The relationship between pneumonia and heart failure (HF) appears bidirectional with pneumonia precipitating heart failure (HF) and HF predisposing to it.

Although It’s often quoted that acute respiratory tract infection accounts for 3-16% of patients hospitalized with decompensated heart failure (HF) (based primarily on small observational studies),1 a 2016 large prospective study involving nearly 100,000 HF admission from 305 US hospitals has reported “pneumonia/respiratory process” as the most common precipitating clinical factor, present in 28.2% of cases (arrhythmia and medication noncompliance came in as 2nd and 3rd).2

Interestingly, the same study reported that pneumonia/respiratory process was most prevalent among patients with preserved (≥50%) ejection fraction (EF) compared to those with borderline ( 40%-49%) or reduced (<40%) EF (33% vs 30% vs 24%, respectively). 2

Pulmonary edema may in turn predispose to bacterial pneumonia through adverse effects of edema fluid on lung bacterial defense mechanisms and establishment of a culture medium for bacterial growth by the presence of fluid in the alveolar space.3

So don’t be surprised if you have to treat for both!



  1. Thomsen RW, Kasatpibal N, Riis A, et al. The impact of pre-existing heart failure on pneumonia prognosis: Population-based cohort study. J Gen Intern Med 2008;23:1407-13. https://www.ncbi.nlm.nih.gov/pubmed/18574639
  2. Kapoor JR, Kapoor R, Ju C, et al. Precipitating clinical factors, heart failure characterization, and outcomes in patients hospitalized with heart failure with reduced, borderline, and preserved ejection fraction. JACC 2016;4:464-72. https://www.scholars.northwestern.edu/en/publications/precipitating-clinical-factors-heart-failure-characterization-and 
  3. Harris GD, Woods DE, Fine R, et al. The effect of intraalveolar fluid on lung bacterial clearance. Lung 1980; 158;91-100 Harris GD, Woods DE, Fine R, et al. The effect of intraalveolar fluid on lung bacterial clearance. Lung 1980; 158;91-100. https://link.springer.com/article/10.1007/BF02713708
My patient with acute exacerbation of heart failure and pulmonary edema also has pneumonia. How often do heart failure and pneumonia coexist?

My patient with aortic sclerosis has a loud systolic ejection murmur. What is the exact mechanism of this murmur?

We usually blame cardiac murmurs on the “turbulence” caused by blood flowing past an irregular valve surface but, believe it or not, how the murmur is created has been a matter of controversy. 1-4

For sure, murmurs are generated by disturbance of laminar blood flow (ie, turbulence) but over the years many have argued that turbulence per se fails to produce adequate acoustic force to be audible at the chest wall.2 Although challenged by some,1  the concept of “vortex shedding” borrowed from fluid dynamics is fascinating and has been proposed as a potential explanation.

Per this theory, just as a boulder causes a stream to separate and generate vortices, valves (particularly when abnormal) also create vortices. As the vortices are shed near the valve, they leave in their place relatively calm wakes which are then rapidly filled by flowing blood, creating the sound of a murmur.  

Two important variables in this theory are velocity and viscosity. When the velocity of blood flow increases substantially as in high cardiac output states (eg, fever, pregnancy), vortex shedding and the intensity of the murmur also increase. Similar phenomenon may be expected when the blood viscosity is lowered (eg, in anemia).



  1. Sabbah HN, Stein PD. Turbulent blood flow in humans: Its primary role in the production of ejection murmurs. Circ Res 1976;38: 513-24. https://www.ncbi.nlm.nih.gov/pubmed/1269101
  2. Alpert MA, Systolic murmurs. In Walker HK, Hall WD, Hurst JW. Clinical methods: The history, physical, and laboratory examinations. 3rd ed. Butterworths, Boston, 1990. https://www.ncbi.nlm.nih.gov/books/NBK345/
  3. Bruns D. A general theory of the causes of murmurs in the cardiovascular system. Am J Med 1959;27:360-74. http://www.amjmed.com/article/0002-9343(59)90002-6/fulltext
  4. Guntheroth WG. Innocent murmurs: A suspect diagnosis in non-pregnant adults. Am J Cardiol 2009;104:735-7. https://www.ncbi.nlm.nih.gov/pubmed/19699354
My patient with aortic sclerosis has a loud systolic ejection murmur. What is the exact mechanism of this murmur?