COMMENTARY

Cardiology 2028: Predicting the Future

Melissa Walton-Shirley, MD

Disclosures

August 28, 2018

Milton Packer opened the session with the following statement: "The purpose of making predictions is not to be right but to luxuriate in the power of human imagination." Who to better lead our imaginations than some of the most innovative minds in cardiology? During this session, Milton Packer (Dallas, Texas), Eugene Braunwald (Boston, Massachusetts), Gerhard Hindricks (Leipzig, Germany), and Paul Ridker (Boston) were allowed to unleash their creativity without constraint. Their task, or rather their pleasure, was to paint a vivid picture of cardiology 10 years into the future.

Packer tried to convince the audience that most of his predictions won't come true, but his enthusiasm and detailed descriptions betray that statement. He started with a prediction that autophagy will become a therapy for reduced systolic ejection fraction heart failure. This induction of cellular housekeeping rids cells of unwanted proteins, viruses, and suborganelles, a process important in aging and the development of countless diseases. He based this information on studies in which deletion of autophagy genes results in experimental cardiomyopathy models. Indeed, he states, "We already have drugs that seem to promote the process such as metformin, SGLT2s, and rapamycin." It all seems plausible.

Packer also believes that heart failure with preserved ejection fraction (HFpEF) will be divided into three basic subgroups driven by different mechanisms: abnormal genetic coding for elasticity proteins, abnormal protein accumulation, and fibrosis as a result of chronic inflammation. Obesity-related HFpEF is related to epicardial inflammation. He pitches inhibitors of mineralocorticoid, sodium/glucose cotransporter 2 (SGLT2), and neprilysin as possible selective therapies.

He also predicted that heart failure will no longer be managed by cardiologists and maybe not even by physicians but rather by highly specialized nurse practitioners. Packer warned that the production of new heart failure meds will cease because of cost. He predicts that cell- and gene-based therapies will fail; however, the proliferation of mechanical devices will mean that "No one with financial resources will die of heart failure involuntarily."

Eugene Braunwald was the next to peer into the cardiovascular crystal ball. He predicts that gadolinium-free cardiac MR (CMR) stress testing will be used to distinguish epicardial from microvascular coronary artery disease. "There are many patients with ischemic heart disease who do not have epicardial obstruction, particularly women," he said. He also believes that the price of hybrid positron emission tomography combined with MRI will be driven down. He demonstrated the beauty of displaying simultaneously metabolism, perfusion, inflammation, and myocardial microcalcification in a single scan.

Braunwald then spoke about his confidence that genetic risk scores will be used to predict clinical benefit of therapies. He flashed a slide of the Lancet 2015 paper[1] that demonstrated how risk scoring predicted statin efficacy in primary and secondary prevention. "They say you can't treat everyone in the country with a statin. The polygenic risk score will help you find who will benefit from a statin," he said.

Finally, he projected the use of a primary prevention "vaccine." He treated us to a slide showing how years of elevated low-density lipoprotein cholesterol (LDL-C) can produce coronary artery disease.[2] People who are homozygous for familial hypercholesterolemia (FH) have LDL-C levels in the 750-mg/dL range and manifest disease by age 12 years. Heterozygotes have LDL-C levels around 200 mg/dL and manifest disease around age 35 years; those of us without FH and levels of LDL-C of 105 mg/dL ("A level much higher than mine," he quipped) manifest disease at the average age of 70 years. The compound inclisiran  will be our answer. "You see a robust 40% sustained LDL-C reduction with a single injection once per year. You could couple it with a flu shot he," he said.

Next, we heard the future of arrhythmia management from Hindricks. He encouraged us to literally and figuratively "think horizontal." He showed us a picture of his 500-bed hospital that performs 24,000 interventions per year. "It's a vertical structure, same as the Prussian military," he said. He doesn't think that is optimal to serve patients because we need to be connected in multiple fashions and in ways important for disease management, with both inpatient and outpatient reach. He asks us to encourage our friends and mentorees to work in integrated data process monitoring to gain insight into these processes and developments.

Hindricks predicted that huge amounts of lifestyle and health data will be generated by wearables but cautioned us to remember that "measuring doesn't change outcome." Machine learning will generate algorithms that will impact outcomes. He also believes that CMR will become a key technology and will be available in most cardiology units. "In patients with A-fib who ask, 'What will be my outcome from catheter intervention?', CMR will stratify the success rate as low, moderate, or high by revealing the degree of atrial fibrosis. It will also improve the success of intervention for catheter ablation as requiring an endocardial vs an epicardial approach. "You can personalize treatment," he said.

He gave one last piece of advice: "Get your colleagues to go into CMR."

Then Paul Ridker stepped to the microphone. He started by saying that "Precision medicine is not personalized medicine." He quoted Leopold and Loscalzo's definition: "Precision medicine is an integrative approach to CV disease prevention and treatment that considers an individual's genetics, lifestyle and exposures as determinants of their cardiovascular health and disease phenotypes." Ridker was emphatic that "Populations are NOT patients. Those patients in front of us have endophenotypic characteristics. We must address how they are different and then select their therapies. There is no average patient, at least not in my clinic."

He predicted that therapies for diabetes will be based on five different types, as outlined in a recent Lancet publication.[3] Time to chronic kidney disease, microalbuminuria, and development of coronary artery disease vary among these subgroups, and therefore monitoring and treatments will vary as well.

He also believes we will take diet and lifestyle modification to the streets. He points to the Black Barbershop trial,[4] wherein promotion of blood pressure monitoring by barbers and therapy prescribed by pharmacists reduced blood pressure. He pointed out that this type of community-based program "requires an investment outside the hospital." He has led by example, having already founded a community wellness center where medical residents come to give lectures on topics such as opioid abuse and cholesterol lowering.

Ridker discussed the future of glucose control devices, referencing a recent New England Journal of Medicine article[5] reporting on the entire process of glucose testing and insulin delivery as a closed loop (artificial pancreas) handled without requiring much input from patients. In that trial of 136 patients,  those in the closed-loop group had higher rates of optimal glucose control (66% vs 41%) with no severe hypoglycemia compared with those under best nursing care.

He then said that the real challenges are going to be international global health and that leadership from Europe will be absolutely crucial. "Global warming and consequent human migration will become a medical issue. We've got to communicate clearly scientific fact from nonscientific fact. We are up against some challenges, though," he concluded.

Carl Sagan once said, "Imagination will often carry us to worlds that never were. But without it we go nowhere." Thanks to the depths of the human imagination on display during today's talk at ESC 2018, we are most definitely going somewhere.

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