Milton Packer M.D.

Posted June 15th 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.

Milton Packer M.D.

Milton Packer M.D.

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].

Full text of this article.

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.)


Posted May 15th 2019

Neurohormonal and Transcatheter Repair Strategies for Proportionate and Disproportionate Functional Mitral Regurgitation in Heart Failure.

Milton Packer M.D.

Milton Packer M.D.

Packer, M. and P. A. Grayburn (2019). “Neurohormonal and Transcatheter Repair Strategies for Proportionate and Disproportionate Functional Mitral Regurgitation in Heart Failure.” JACC Heart Fail May 3. [Epub ahead of print].

Full text of this article.

Functional mitral regurgitation (MR) is present to varying degrees in most patients with chronic heart failure (HF) and left ventricular (LV) systolic, and in ~ 30% its magnitude is hemodynamically meaningful. A critical determinant of MR in these patients is the degree of LV dilatation. Remodeling and enlargement of the LV leads to displacement of the papillary muscles and widening and flattening of the mitral annulus, which (together with a reduction in closing forces) impairs the coaptation of the mitral valve (MV) leaflets. However, independent of LV end-diastolic volume (LVEDV), ventricular dyssynchrony contributes importantly to functional MR. In patients with meaningful QRS prolongation, dyssynchrony causes unequal contraction of papillary muscle bearing walls, preventing coordinated closure of the MV leaflets; amelioration of the conduction delay by cardiac resynchronization reduces MR. Additionally, irrespective of the presence of electric conduction delay, localized LV remodeling can cause apical and posterior displacement of the papillary muscles and dysschronous contraction of the leaflet-supporting structures independent of global LV dysfunction. (Excerpt from text of article-in-press, not paginated; no abstract available.)


Posted May 15th 2019

Contrasting Effects of Pharmacological, Procedural and Surgical Interventions on Proportionate and Disproportionate Functional Mitral Regurgitation in Chronic Heart Failure.

Milton Packer M.D.

Milton Packer M.D.

Packer, M. and P. A. Grayburn (2019). “Contrasting Effects of Pharmacological, Procedural and Surgical Interventions on Proportionate and Disproportionate Functional Mitral Regurgitation in Chronic Heart Failure.” Circulation May 1. [Epub ahead of print].

Full text of this article.

Two distinct pathways can lead to functional mitral regurgitation (MR) in patients with chronic heart failure and a reduced ejection fraction. When remodeling and enlargement of the left ventricle (LV) causes annular dilatation and tethering of the mitral valve leaflets, there is a linear relationship between LV end-diastolic volume and the effective regurgitant orifice area (EROA) of the mitral valve. These patients – designated as having proportionate MR – respond favorably to treatments that lead to reversal of LV remodeling and a decrease in LV volumes (e.g., neurohormonal antagonists and LV assist devices), but they may not benefit from interventions that are directed only at the mitral valve leaflets (e.g., transcatheter mitral valve repair). In contrast, when ventricular dyssynchrony causes functional MR due to unequal contraction of the papillary muscles, the magnitude of regurgitation is greater than that predicted by LV volumes. These patients – designated as having severe but disproportionate MR – respond favorably to treatments that are directed to the mitral valve leaflets or its supporting structures (e.g., cardiac resynchronization or transcatheter mitral valve repair), but they may derive little benefit from interventions that act only to reduce LV cavity size (e.g., pharmacological treatments). This novel conceptual framework reflects the important interplay between LV geometry and mitral valve function in determining the clinical presentation of patients, and it allows characterization of the determinants of functional MR to guide the most appropriate therapy in the clinical setting.


Posted May 15th 2019

Is Any Patient With Chronic Heart Failure Receiving the Right Dose of the Right Beta-Blocker in Primary Care?

Milton Packer M.D.

Milton Packer M.D.

Packer, M. (2019). “Is Any Patient With Chronic Heart Failure Receiving the Right Dose of the Right Beta-Blocker in Primary Care?” Am J Med Apr 12. [Epub ahead of print].

Full text of this article.

Are physicians prescribing the right beta-blockers in the right way to patients with chronic heart failure and a reduced ejection fraction? Beta-blockers carry the strongest possible level of recommendations in guideline documents throughout the world. Yet, numerous surveys have shown that this class of drugs is greatly underutilized in clinical practice, particularly amongst primary care physicians in the US. In the most recently published survey, amongst primary care physicians, fewer than 10% of patients with heart failure who had no contraindication to beta-blockade and should have been treated with a beta-blocker actually were prescribed an evidence-based beta-blocker at the right dose. The news might even be worse, because the survey did not evaluate whether the use of these drugs in patients with atrial fibrillation was appropriate. Internists and family physicians are responsible for the care of most patients with chronic heart failure in the United States. If they are not prescribing life-saving drugs in the right manner, then millions of people with a highly treatable disease and highly preventable cause of death are receiving suboptimal therapy. The benefits of beta-blockers are remarkable and not controversial. The strongest possible evidence supporting their widespread use has been available to the clinical community for more than 15 years. Furthermore, the recommended formulations are generic and inexpensive and do not require preauthorization or complicated preapprovals. It is time for primary care organizations to sound the alarm. Heart failure is the most common, most serious and most responsive disorder that community-based practitioners can treat without the need for complex testing or referral for subspecialist care. What are we waiting for? (Excerpt from text of article-in-press, not paginated; no abstract available.)


Posted May 15th 2019

Disproportionate functional mitral regurgitation: a new therapeutic target in patients with heart failure and a reduced ejection fraction.

Milton Packer M.D.

Milton Packer M.D.

Packer, M. (2019). “Disproportionate functional mitral regurgitation: a new therapeutic target in patients with heart failure and a reduced ejection fraction.” Eur J Heart Fail Apr 24. Epub ahead of print].

Full text of this article.

Patients with chronic heart failure and a reduced ejection fraction who have severe and disproportionate mitral regurgitation (MR) are likely to experience important clinical consequences resulting from the haemodynamic stresses imposed by the regurgitant lesion, and the severity of MR is not likely to be reduced by conventional therapy with neurohormonal antagonists, even when administered in maximally tolerated doses. Such patients should first be treated with cardiac resynchronization (if they qualify for the procedure), and non‐candidates and non‐responders should be seriously considered for transcatheter mitral valve repair. Therefore, when treating heart failure with a reduced ejection fraction, it is now time for physicians to identify patients who also have severe and disproportionate MR, because they require specialized procedures beyond optimal pharmacological therapy. (Excerpt from text, p. 2-3; no abstract available.)