Cardiology

Packer, M. (2019). “Are healthcare systems now ready to adopt sacubitril/valsartan as the preferred approach to inhibiting the renin-angiotensin system in chronic heart failure? The culmination of a 20-year journey.” Eur Heart J May 23. [Epub ahead of print].

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Do the effects of neprilysin inhibition on high-sensitivity troponin T and soluble ST2 advance our management of heart failure? It is always gratifying to see biomarkers change in a favourable direction, but such changes do not reliably identify the true mechanism of drug action or quantify the magnitude of the clinical benefits. Furthermore, there are no data to support the use of (or changes in) these biomarkers as a decision tool to select patients for treatment or to determine the appropriate dose for long-term therapy. As one of the two principal investigators of the PARADIGM-HF trial, I was dismayed when obstacles were placed in the path of physicians who sought to prescribe neprilysin inhibition to patients with chronic heart failure. As a matter of personal choice, I have had no financial relationship with the manufacturer of sacubitril/valsartan (Novartis) since the publication of the primary papers, and I have not been involved in any efforts to market or give sponsored presentations on behalf of the drug. However, at the same time, I have been an ardent supporter of the findings of the trial, which represented my second chance (after the disappointment of the OVERTURE trial) to finally demonstrate that neprilysin inhibitors can meaningfully potentiate the survival benefits of conventional antagonists of the renin–angiotensin system in patients with heart failure. If the PIONEER-HF trial allows all cardiologists to embrace that conclusion, I am very pleased. If the biomarker data published in this issue are motivating to practitioners to increase their appropriate prescribing of sacubitril/valsartan, I am delighted to hear that. If physicians, healthcare systems, and the manufacturer are prepared to work collaboratively to facilitate affordable unrestricted access to a life-saving treatment for heart failure, I doubt that patients will complain. (Excerpt from text of this editorial, p. 3; no abstract available.)

Navas, M. C., S. Glaser, H. Dhruv, S. Celinski, G. Alpini and F. Meng (2019). “Hepatitis C Virus Infection and Cholangiocarcinoma: An Insight into Epidemiologic Evidences and Hypothetical Mechanisms of Oncogenesis.” Am J Pathol 189(6): 1122-1132.

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Hepatitis C virus (HCV) infection is a global public health problem because it is a main cause of liver cirrhosis and hepatocellular carcinoma. This human oncogenic virus is also associated with the development of non-Hodgkin lymphoma and cholangiocarcinoma (CCA). The association between HCV infection and CCA has been examined in a number of epidemiologic studies. However, in vivo and in vitro results demonstrating the oncogenic mechanisms of HCV in CCA development and progression are insufficient. Here, we review the epidemiologic association of HCV and CCA and recent publications of studies of HCV infection of cholangiocytes and CCA cell lines as well as studies of viral infection performed with liver samples obtained from patients. In addition, we also discuss the preliminary results of in vitro assays of HCV protein expression in CCA cell lines. Finally, we discuss the hypothetical role of HCV infection in CCA development by induction of epithelial-mesenchymal transition and up-regulation of hedgehog signaling, and consequently biliary tree inflammation and liver fibrosis. Further studies are required to demonstrate these hypotheses and therefore to elucidate the mechanisms of HCV as a risk factor for CCA.

Mack, M. J. and G. W. Stone (2019). “Response to Letters re: The COAPT Trial.” Cardiovasc Revasc Med 20(6): 531-532.

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The COAPT trial was a landmark study that demonstrated for the first time that correction of secondary or functional mitral regurgitation (MR) results in significant clinical benefits in patients with heart failure. The addition of the MitraClip to maximally tolerated guideline-directed medical therapy (GDMT) resulted in a 47% reduction in hospitalization for heart failure, the primary endpoint at two years. In addition, there were significant 2-year improvements in survival, quality-of-life and exercise performance. We appreciate the great interest generated by the COAPT outcomes as reflected by the letters to the editor in this issue. They raise some salient points that we would like to address. Khan et al. note that in COAPT, there was significant up-titration of both beta-blockers and mineralocorticoid receptor antagonists (MRA) during follow-up in the device arm. The protocol intent was to maintain GDMT in both arms, and as reported, there were few major increases or reductions in medical therapy in both groups. However, MR reduction by the MitraClip increases cardiac output and blood pressure, enabling up-titration of medical therapy in some patients. These medication changes, which might be expected in real-world practice, may have contributed in small part to the therapeutic benefit in the device arm. However, we do not agree with the authors that a double-blinded sham-controlled study is required to mitigate this potential “bias” (which is actually a response to improved hemodynamics, not bias). The beta-blocker increase was transient (1-year timepoint only), and the MRA difference was small and not significant. Nitrate use at 1 and 2 years was actually more common in the control arm. These modest changes in medications cannot explain the marked absolute benefits of MR reduction observed in COAPT (number needed-to-treat 3 and 6 patients, respectively, to prevent one hospitalization and save one life within 2 years). Given these outcomes, it would be both unfeasible and unethical to conduct a sham-controlled study in which a group of patients meeting COAPT-eligibility criteria were not offered active treatment. (Excerpt from text, p. 531; no abstract available.)

DeRose, J. J., Jr., D. M. Mancini, H. L. Chang, M. Argenziano, F. Dagenais, G. Ailawadi, L. P. Perrault, M. K. Parides, W. C. Taddei-Peters, M. J. Mack, D. D. Glower, B. A. Yerokun, P. Atluri, J. C. Mullen, J. D. Puskas, K. O’Sullivan, N. M. Sledz, H. Tremblay, E. Moquete, B. S. Ferket, A. J. Moskowitz, A. Iribarne, A. C. Gelijns, P. T. O’Gara, E. H. Blackstone and A. M. Gillinov (2019). “Pacemaker Implantation After Mitral Valve Surgery With Atrial Fibrillation Ablation.” J Am Coll Cardiol 73(19): 2427-2435.

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BACKGROUND: The incidence of permanent pacemaker (PPM) implantation is higher following mitral valve surgery (MVS) with ablation for atrial fibrillation (AF) compared with MVS alone. OBJECTIVES: This study identified risk factors and outcomes associated with PPM implantation in a randomized trial that evaluated ablation for AF in patients who underwent MVS. METHODS: A total of 243 patients with AF and without previous PPM placement were randomly assigned to MVS alone (n = 117) or MVS + ablation (n = 126). Patients in the ablation group were further randomized to pulmonary vein isolation (PVI) (n = 62) or the biatrial maze procedure (n = 64). Using competing risk models, this study examined the association among PPM and baseline and operative risk factors, and the effect of PPM on time to discharge, readmissions, and 1-year mortality. RESULTS: Thirty-five patients received a PPM within the first year (14.4%), 29 (83%) underwent implantation during the index hospitalization. The frequency of PPM implantation was 7.7% in patients randomized to MVS alone, 16.1% in MVS + PVI, and 25% in MVS + biatrial maze. The indications for PPM were similar among patients who underwent MVS with and without ablation. Ablation, multivalve surgery, and New York Heart Association functional (NYHA) functional class III/IV were independent risk factors for PPM implantation. Length of stay post-surgery was longer in patients who received PPMs, but it was not significant when adjusted for randomization assignment (MVS vs. ablation) and age (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.61 to 1.08; p = 0.14). PPM implantation did not increase 30-day readmission rate (HR: 1.43; 95% CI: 0.50 to 4.05; p = 0.50). The need for PPM was associated with a higher risk of 1-year mortality (HR: 3.21; 95% CI: 1.01 to 10.17; p = 0.05) after adjustment for randomization assignment, age, and NYHA functional class. CONCLUSIONS: AF ablation, multivalve surgery, and NYHA functional class III/IV were associated with an increased risk for permanent pacing. PPM implantation following MVS was associated with a significant increase in 1-year mortality. (Surgical Ablation Versus No Surgical Ablation for Patients With Atrial Fibrillation Undergoing Mitral Valve Surgery; NCT00903370).

Blankenship, J. C., J. W. Choi, T. S. Das, P. M. McElgunn, D. Mukherjee, L. L. Paxton, R. Piana, J. R. Sauer, C. J. White and P. L. Duffy (2019). “SCAI/ACVP expert consensus statement on cardiovascular catheterization laboratory economics: If the cath lab is your home you should understand its finances: This statement was endorsed by the Alliance of Cardiovascular Professionals (ACVP) in April 2019.” Catheter Cardiovasc Interv May 19. [Epub ahead of print].

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This article is intended for any physician, administrator, or cardiovascular catheterization laboratory (CCL) staff member who desires a fundamental understanding of finances and economics of CCLs in the United States. The authors’ goal is to illuminate general economic principles of CCL operations and provide details that can be used immediately by CCL leaders. Any article on economics in medicine should start by acknowledging the primacy of the principles of medical ethics. While physicians have been trained to act in the best interests of their patients and avoid actions that would harm patients it is vitally important that all professionals in the CCL focus on patients’ needs. Caregivers both at the bedside and in the office must consider how their actions will affect not only the patient they are treating at the time, but others as well. If the best interests of a patient were to conflict with any recommendation in this article, the former should prevail. KEY POINTS: To be successful and financially viable under current payment systems, CCL physicians, and managers must optimize the outcomes and efficiency of care by aligning CCL leadership, strategy, organization, processes, personnel, and culture. Optimizing a CCL’s operating margin (profitability) requires maximizing revenues and minimizing expenses. CCL managers often focus on expense reduction; they should also pay attention to revenue generation. Expense reduction depends on efficiency (on-time starts, short turn-over time, smooth day-to-day schedules), identifying cost-effective materials, and negotiating their price downward. Revenue optimization requires accurate documentation and coding of procedures, comorbidities, and complications. In fee-for-service and bundled payment reimbursement systems, higher volumes of procedures yield higher revenues. New procedures that improve patient care but are expensive can usually be justified by negotiating with vendors for lower prices and including the “halo effect” of collateral services that accompany the new procedure. Fiscal considerations should never eclipse quality concerns. High quality CCL care that prevents complications, increases efficiency, reduces waste, and eliminates unnecessary procedures represents a win for patients, physicians, and CCL administrators.