Cardiology

Baxter, R. D., J. J. Squiers and J. M. DiMaio (2019). “Commentary: Off-Pump Mitral Repair-Augmenting the Future.” J Thorac Cardiovasc Surg 158(4): e137.

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Functional mitral valve regurgitation continues to greatly increase morbidity and mortality of patients with ischemic cardiac disease. Medical management of mitral regurgitation for this condition can be effective when no other options exist; however, surgical treatment of mitral valve dysfunction for reduction of valvular regurgitation has been shown to increase both quality of life and overall survival in these patients. Operative interventions in this patient population continue to be challenging as a result of decreased physiologic reserve and increased risk of perioperative complications and mortality. In this issue of the Journal, Salizzoni and colleagues describe such a patient in their case report. Repair of this patient’s mitral valve would be complex because of its severe dysfunction and his challenging underlying comorbidities. Traditionally, surgical intervention for this patient could be considered prohibitively risky by many centers. The innovative technique described in this case report, however, offers an interesting approach to this problem. Emerging technologies allow mitral annuloplasty, leaflet edge fixation, and even leaflet tethering in a beating heart without the need for bypass. The most recent innovation—leaflet fixation—has shown great promise in this setting. Currently, however, these options are limited by mitral leaflet and annulus anatomy. Furthermore, a combination of surgical repair options is often needed in this population because of the complex nature of mitral valve anatomy. The technique described in this report, which allowed adequate repair of the mitral valve by leaflet augmentation on a beating heart free of cardiopulmonary bypass, has never been previously described. Proper use of mitral augmentation patches can be challenging for even experienced cardiac surgeons in an on-pump, cardiac arrest scenario. The willingness of the surgeons even to consider performing this procedure on a beating heart is an example of the mindset that has pushed cardiac surgery forward in patient care and technical advancement. The patient described in this case report, a 76-year-old man with significant congestive heart failure and history of multiple coronary artery bypass, is also to be commended. Although he was at high risk in undergoing surgical intervention, he was willing to proceed with a procedure that had never before been performed in a human being. Not only does this reflect his strong desire to alleviate his life-altering symptoms, it also highlights his faith in the surgical team caring for him. His consent to proceed was an essential part in pioneering these new care techniques for other patients with similar pathology. This report describes an innovative surgical technique that may warrant further investigation as we progress from traditional valvular augmentation procedures to minimally invasive techniques. Ongoing development may lead to a method of augmenting valvular tissue through completely endovascular methods and further increase available options for high-risk patients to receive optimal cardiac repair. (Excerpt from text, p. e137; no abstract available.)

Anker, S. D., J. Butler, G. S. Filippatos, W. Jamal, A. Salsali, J. Schnee, K. Kimura, C. Zeller, J. George, M. Brueckmann, F. Zannad and M. Packer (2019). “Evaluation of the Effects of Sodium-Glucose Co-Transporter 2 Inhibition with Empagliflozin on Morbidity and Mortality in Patients with Chronic Heart Failure and a Preserved Ejection Fraction: Rationale for and Design of the Emperor-Preserved Trial.” Eur J Heart Fail Sep 16. [Epub ahead of print].

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BACKGROUND: The principal biological processes that characterize heart failure with a preserved ejection fraction (HFpEF) are systemic inflammation, epicardial adipose tissue accumulation, coronary microcirculatory rarefaction, myocardial fibrosis and vascular stiffness; the resulting impairment of left ventricular and aortic distensibility (especially when accompanied by impaired glomerular function and sodium retention) causes increases in cardiac filling pressures and exertional dyspnoea despite the relative preservation of left ventricular ejection fraction. Independently of their actions on blood glucose, sodium-glucose co-transporter 2 (SGLT2) inhibitors exert a broad range of biological effects (including actions to inhibit cardiac inflammation and fibrosis, antagonize sodium retention and improve glomerular function) that can ameliorate the pathophysiological derangements in HFpEF. Such SGLT2 inhibitors exert favourable effects in experimental models of HFpEF and have been found in large-scale trials to reduce the risk for serious heart failure events in patients with type 2 diabetes, many of whom were retrospectively identified as having HFpEF. STUDY DESIGN: The EMPEROR-Preserved Trial is enrolling approximately 5750 patients with HFpEF (ejection fraction >40%), with and without type 2 diabetes, who are randomized to receive placebo or empagliflozin 10 mg/day, which is added to all appropriate treatments for HFpEF and co-morbidities. STUDY AIMS: The primary endpoint is the time-to-first-event analysis of the combined risk for cardiovascular death or hospitalization for heart failure. The trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all-cause mortality and recurrent hospitalization events, and will assess a wide range of biomarkers that reflect important pathophysiological mechanisms that may drive the evolution of HFpEF. The EMPEROR-Preserved Trial is well positioned to determine if empagliflozin can have a meaningful impact on the course of HFpEF, a disorder for which there are currently few therapeutic options.

Mack, M. J. (2019). “RESPONSE: Adapting to Change in a Time of Uncertainty.” J Am Coll Cardiol 74(6): 816-817.

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Historically, the specialty of thoracic surgery has always been, as Han states, one of “paradigm shifts” or, as euphemistically referred to within the specialty, “staying one operation ahead of extinction.” To wit, the specialty began as one to treat tuberculosis until the introduction of sulfa drugs greatly diminished the role of surgery for that disease. The specialty then evolved to the management of rheumatic heart disease for which surgery was a mainstay of treatment until penicillin dramatically reduced the incidence of the disease in developed countries. Next, the central role of surgical coronary revascularization in the treatment of coronary artery disease was significantly modulated by the introduction of percutaneous coronary intervention. Furthermore, many other procedures began as thoracic and cardiac surgical procedures, including bronchoscopy, esophagoscopy, permanent pacemaker, defibrillator implantation, and insertion of intra-aortic balloon pumps, only to have those procedures move to other specialties as the devices become smaller and more easily implanted without general anesthesia. Despite the evolution in the core treatments delivered by our specialty in different eras, we have not become extinct, nor has the specialty diminished; rather, it has survived and thrived . . . As I reflect on the types of operations I was performing when I finished training in 1982, they bear little resemblance to the procedures being performed today. However, that offers little solace to the trainee whose sands are now shifting beneath her/his feet. As the Greek philosopher Heraclitus stated, “the only constant is change.” You cannot worry too much that you chose the wrong career path or succumb to the fear that you will be left behind. Rather, embrace what you love to do and be cognizant of the changes in the ecosystem in which you work. Learn to lead change, embrace that which is currently good, have the vision to determine what needs to change, and have the wisdom to know the difference. To paraphrase Charles Darwin, it’s not the strongest of a species that survives, or the most intelligent, but the one most responsive to change. (Excerpts from text, p. 816-817.)

Thuijs, D., A. P. Kappetein, P. W. Serruys, F. W. Mohr, M. C. Morice, M. J. Mack, D. R. Holmes, Jr., N. Curzen, P. Davierwala, T. Noack, M. Milojevic, K. D. Dawkins, B. R. da Costa, P. Juni and S. J. Head (2019). “Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial.” Lancet Aug 30. [Epub ahead of print].

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BACKGROUND: The Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial was a non-inferiority trial that compared percutaneous coronary intervention (PCI) using first-generation paclitaxel-eluting stents with coronary artery bypass grafting (CABG) in patients with de-novo three-vessel and left main coronary artery disease, and reported results up to 5 years. We now report 10-year all-cause death results. METHODS: The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension of follow-up of a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries. Patients with de-novo three-vessel and left main coronary artery disease were randomly assigned (1:1) to the PCI group or CABG group. Patients with a history of PCI or CABG, acute myocardial infarction, or an indication for concomitant cardiac surgery were excluded. The primary endpoint of the SYNTAXES study was 10-year all-cause death, which was assessed according to the intention-to-treat principle. Prespecified subgroup analyses were performed according to the presence or absence of left main coronary artery disease and diabetes, and according to coronary complexity defined by core laboratory SYNTAX score tertiles. This study is registered with ClinicalTrials.gov, NCT03417050. FINDINGS: From March, 2005, to April, 2007, 1800 patients were randomly assigned to the PCI (n=903) or CABG (n=897) group. Vital status information at 10 years was complete for 841 (93%) patients in the PCI group and 848 (95%) patients in the CABG group. At 10 years, 244 (27%) patients had died after PCI and 211 (24%) after CABG (hazard ratio 1.17 [95% CI 0.97-1.41], p=0.092). Among patients with three-vessel disease, 151 (28%) of 546 had died after PCI versus 113 (21%) of 549 after CABG (hazard ratio 1.41 [95% CI 1.10-1.80]), and among patients with left main coronary artery disease, 93 (26%) of 357 had died after PCI versus 98 (28%) of 348 after CABG (0.90 [0.68-1.20], pinteraction=0.019). There was no treatment-by-subgroup interaction with diabetes (pinteraction=0.66) and no linear trend across SYNTAX score tertiles (ptrend=0.30). INTERPRETATION: At 10 years, no significant difference existed in all-cause death between PCI using first-generation paclitaxel-eluting stents and CABG. However, CABG provided a significant survival benefit in patients with three-vessel disease, but not in patients with left main coronary artery disease. FUNDING: German Foundation of Heart Research (SYNTAXES study, 5-10-year follow-up) and Boston Scientific Corporation (SYNTAX study, 0-5-year follow-up).

Packer, M. (2019). “Why Are Physicians So Confused about Acute Heart Failure?” New England Journal of Medicine 381(8): 776-777.

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For most of the past 3000 years, physicians believed that all patients with heart failure had acute heart failure. Heart failure was viewed as an episodic disorder — that is, patients were considered to have heart failure when they presented with fluid retention, and they no longer had heart failure after diuresis. The chronicity of heart failure was recognized only when invasive and noninvasive measurements showed severe ongoing structural and functional abnormalities between episodes. To develop approaches to preventing hospitalizations and minimizing the functional and prognostic consequences of heart failure, clinical investigators needed to focus on the underlying disease process. Extensive research beginning in the 1980s established that combination therapy with neurohormonal antagonists reverses ventricular remodeling, improves functional capacity, and reduces the risk of disease progression and death. However, use of these drugs in primary care has been distinctly suboptimal, possibly because physicians have been inclined to discount the importance of intensive treatment for a disease whose progression is typically clinically silent. Instead, practitioners have focused on the treatment of worsening episodes that require hospitalization . . . However, most patients who are hospitalized with worsening heart failure do not have a new, acute disorder. Instead, they present with decompensation of chronic underlying ventricular dysfunction as a consequence of gradual but progressive increases in cardiac filling pressures in the preceding weeks. Sometimes the deterioration is triggered by cardiac arrhythmia or pulmonary infection, but typically the deterioration is not sudden or immediately life-threatening. Are these episodes of worsening heart failure a medical emergency akin to acute pulmonary edema decades ago? Most patients recover within a few days after intensification of medical therapy. However, these events are often accompanied by the early release of troponin, indicating a small degree of myocardial injury that is possibly related to acute ventricular distention. Could emergency interventions to reduce volume overload salvage a few cardiomyocytes, which might (in turn) have benefits for long-term prognosis? We know that each hospitalization accelerates the rate of progression of heart failure. So, is decompensated heart failure similar to an acute coronary syndrome, for which it is critical to perform an emergency intervention to minimize irreversible cardiac injury? The hypothesis that exceptionally early short-term therapy during a hospitalization for heart failure might yield long-term benefits was supported by the findings of the Relaxin in Acute Heart Failure (RELAX-AHF) trial. In that trial, a 48-hour infusion of the vasodilator serelaxin decreased the release of troponin and resulted in a remarkable 37% lower risk of death during the subsequent 6 months than placebo. However, because the benefit with respect to mortality was based on a sparse number of deaths, it was greeted with great skepticism. Outsized mortality benefits that have been observed in underpowered phase 2 trials in patients with heart failure often have not been subsequently confirmed in definitive phase 3 trials . . . Hospitalization for worsening symptoms is an important event in chronic heart failure; it identifies patients with particularly rapid advancement of the underlying disorder. However, decompensation is not an acute illness or an indicator of subclinical myocardial injury that requires emergency intervention with a novel treatment; the acute elevation of troponin level may subside, but the troponin level remains elevated after hospital discharge. Although it is important to achieve clinical stabilization, it is more critical to ensure that patients are treated vigorously between hospitalizations to decrease the risk of readmission and death. A focus on intensive outpatient care (rather than an obsession with inpatient therapy) is needed to reduce the burden of heart failure. (Excerpts from text, p. 776-777; no abstract available.)