In Conversation with Jay Norman Cohn MD

Hector Ventura, MD, writes…

One of the highlights of my professional career was the chance to meet and to get to know Dr Cohn. The first time I met him I did not know that I would become, like him, president of ISCP in 2020. I saw him in 2019 at the Heart Failure Society annual meeting and I invited him to receive the life time achievement award from ISCP at the meeting in 2020. He was proud to accept and very happy to know that I was the president elect of ISCP. I was looking forward to having him with us in Miami, however circumstances as we know did not allow us to have the annual meeting. I called him to let him know that we wanted to highlight his professional contributions on our website and he was elated. I also wished him a very happy birthday and told him that it was amazing that he continues full speed to find pathways to manage and prevent heart disease. Thank you, Jay, for all you have done.

Hector Ventura, MD: First, Dr. Cohn would you describe how you became interested in heart failure?

Jay N Cohn, MD: “I suspect that the reason I became interested in heart failure as a syndrome grew out of my interests in hypertension because that was where I began.  We were looking for a mechanism of hypertension, that it is why is the blood vessel constricted and there were all kinds of laboratories trying to demonstrate activation of the human renin angiotensin system and activation of the sympathetic nervous system as causes for hypertension.  The data to support those mechanisms were very weak.  It was so hard to show that there was sympathetic activation in hypertension and the renin-angiotensin system wasn’t activated in most people with hypertension.  So, here we had a blood vessel that was constricted and we didn’t have a good explanation for why that was the case.  When we recognized that failure of the left ventricle could be favorably effective by drugs which we relaxed the blood vessels, I realized here is another syndrome in which the blood vessels are constricted.  The reason the blood pressure is not elevated is that the heart is weak.  So, in many respects, heart failure had the same pathophysiology as hypertension, but with a weakened heart… So, my interest really didn’t begin with a patient who had heart failure, my interest began with the intellectual curiosity about what controls the blood vessel and how the blood vessel affects the heart…”

Hector Ventura: Let me asked you about the use of vasodilatory agents to treat heart failure. During my training in Argentina I was working under the supervision of Esteban Mikulic, MD, an Argentinean physician who trained with you, who after coming back from his training told us about how you came to use nitroprusside in the treatment of heart failure. Could you tell me how did it happen?

Jay N Cohn, MD “Well, this grew out our hypertension research.  We were studying severe hypertension and I identified when we put a catheter in the left ventricle…the patient had a very high left ventricular end-diastolic pressure and it occurred to me, is this high pressure in the left ventricle just a result of the high blood pressure or is this intrinsic cardiac disease.  So, I felt that we needed to use a drug, which would acutely drop blood pressure without having a direct effect on the heart… The people at Cleveland Clinic, Dr Irvin Page, had described some data with nitroprusside and you had to put it in powder form, from a chemical company, and mix it up into a solution to inject.  We did that and we also did some studies on isolated canine myocardium to demonstrate that when we put nitroprusside in, it had no direct effect on the myocardium at all.  So, we felt that this vasodilator did not have a direct cardiac effect.  Then we did a series of patients in which we acutely lowered blood pressure with nitroprusside.  Even before the blood pressure started to fall, there was a big drop in left ventricular end-diastolic pressure and it occurred to me that this drug is doing something even beyond blood pressure reduction to improve the performance of the left ventricle.  Well, it took us some years to realize that it was increasing the compliance of the artery and it took us to develop pulse contour analysis before we were able to demonstrate what nitroprusside is doing.  But at that time, it was clear that the vascular effects of nitroprusside, which is all that the drug was doing, was somehow favorably affecting the performance of the left ventricle and it was the link between the periphery and the heart which hadn’t been described then.  Nobody had really even looked at it and the cardiac output went up, so it was not just a preload affect, it was indeed an effect on the performance of the left ventricle.  Then I said, well gee if this works this well in hypertensives who are not in heart failure overtly, maybe it would work in people in heart failure even though they are not hypertensive, because if you can improve the performance of the left ventricle with this drug, we ought to give it to people who have severe heart failure.  So, we started in some patients with acute myocardial infarction, who were in severe pump failure and were oliguric, in cardiogenic shock, and really dying of their pump failure.  We went to the bedside, we plopped this catheter, we injected nitroprusside, and they got immediately better.  The blood pressure didn’t even fall very much.  We were getting a tremendous effect on performance of the left ventricle without even significant falling of blood pressure.  So, that began the whole saga of vasodilators and, then of course, we wanted to find an oral drug which could do the same thing and that’s when we started the isosorbide dinitrate studies. That’s how I got interested in using vasodilators in heart failure, through trying to gain insight into how the left ventricle and the vasculature work together to maintain circulatory integrity…”