Pacemaker Optimization Mechanisms in the Spectrum of Cardiac Disease Rationale to Protocol

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Philip Houck offers a comprehensive overview of the vast range of device programming options, highlighting the importance of a targeted approach for optimal outcomes. An enjoyable read.

The paper just needs small modifications in its organization. For instance, 1. Is the introduction, but then followed by a long discussion concerning disease processes, echo evaluation, pacing goals, mathematical equations, and then 2. Is the problem which is a short paragraph, and 3. Optimization, and 4. Conclusion. Perhaps reorganize each of the headings here so that is is more clear for the reader. Eg. Introduction, Disease Processes, Echo Evaluation of disease processes.

Page 3: Spectrum of Cardiac Disease.

Should be modified into a table for easier flow for readers.

Line 178 – a little unclear. Either remove this paragraph, or perhaps should be titled ‘Right heart failure’ – and suggest its optimization (as opposed to discussing left-sided failure here). Although increased frequency of pacing the RV may similarly be detrimental…

Suggest to modify the conclusion for improved clarity.

Author Response

Response to reviewer 1

Philip Houck offers a comprehensive overview of the vast range of device programming options, highlighting the importance of a targeted approach for optimal outcomes. An enjoyable read.

I appreciate the effort of the reviewers to improve this paper.  I have made the changes they have suggested.

The paper just needs small modifications in its organization. For instance, 1. Is the introduction, but then followed by a long discussion concerning disease processes, echo evaluation, pacing goals, mathematical equations, and then 2. Is the problem which is a short paragraph, and 3. Optimization, and 4. Conclusion. Perhaps reorganize each of the headings here so that is is more clear for the reader. Eg. Introduction, Disease Processes, Echo Evaluation of disease processes.

Heading were renamed as above

Page 3: Spectrum of Cardiac Disease.

Should be modified into a table for easier flow for readers.

Table inserted

Line 178 – a little unclear. Either remove this paragraph, or perhaps should be titled ‘Right heart failure’ – and suggest its optimization (as opposed to discussing left-sided failure here). Although increased frequency of pacing the RV may similarly be detrimental…

I am not sure of line 178 since my copy does not have lines

I did change heading for clarity Right heart failure in the setting of left heart failure or pulmonary hypertension

I also made the following change

The spectrum of cardiac disease adds intricacy requiring different optimization goals.  Early pacemakers and more modern pacemakers have not accounted for two hearts, a right and a left heart.  The failure of either heart will result in morbidity and mortality in the patient.  Failure of the left heart eventually causes failure of the right heart.  This means the pacing strategy may need to change as heart function evolves.  The function of current devices is to improve right heart function by improving left heart function with a left ventricular lead.  If this fails and right heart dysfunction is the dominant reason for symptoms, right ventricular pacing may be needed.  The left sided strategy leaves some patients with advanced disease and primary right heart failure no options for improvement.  Cascaded pacing, currently not available could salvage some of these patients.  Priming the left heart with right ventricular pacing for several beats and then switching to left ventricular pacing in an alternating sequence is one possible solution to combined left and right heart failure.

I had suggested this cascaded pacing to manufactures but seemed uninterested

Suggest to modify the conclusion for improved clarity.  As below

8. 8. Conclusion

The problem can be stated as over 3 billion choices to improve 14 disease states with 9 optimization goals (some of the optimization goals are diametrically opposed) to improve dyspnea, shortness of breath, fatigability, exercise intolerance, edema, swelling, fluid retention, and arrhythmias.  The goal is to increase Left Ventricular Outflow Integral, reduce mitral regurgitation, increase longitudinal conduction velocities and restore synchrony of the septum to the ventricle that needs it the most.  Pacemakers are sophisticated devices that should be optimized to meet the goals of individual patients.  Pacing trials provided the basic justification for an additional pacing lead but fall short in optimizing individual patients.  The physician needs to recognize the spectrum of disease and use the protocol to improve the quality of life of the individual patient.  Age and pacemakers are highly correlated.  The aged have special heart rate needs to prevent falls from orthostatic hypotension and fatigue due to reduced cardiac output.  The protocol will help select the most optimum pacing parameters out of the 3,875,040,000 choices.  Caveat – As the heart remodels with the new pacing parameters repeat optimization may be required. Do not trust device manufacturer’s algorithms in symptomatic patients.

Response to reviewer 2

This paper is extremely interesting , focusing on Pacemaker Optimization Mechanisms in the Spectrum of Cardiac Disease. Paper is well written, I have only one minor comment in order to improve the manuscript. Authors should  more focus and discuss about how the quality of life as well as older age should be both considered on pacemaker optimization mechanisms. s. The number of very elderly patients receiving pacemakers is increasing and little is known about survival in this specific subgroup, and strong risk factors for all-cause disease may also be non-cardiac. Please cite DOI: 10.1007/s40520-018-1088-5 ; and doi: 10.11909/j.issn.1671-5411.2019.12.010

I have added a special section of age in cardiac spectrums along with references below

Age- Pacemakers are a frequent occurrence in the aged providing improved quality of life [9,10].  The aged have stiff blood vessels and when combined with orthostatic hypotension, the most important parameter to adjust is a higher heart rate

And in conclusion I added

Age and pacemakers are highly correlated.  The aged have special heart rate needs to prevent falls from orthostatic hypotension and fatigue due to reduced cardiac output. 

9. Marini M, Martin M, Saltori M, Quintarelli S, Zilio F, Guarracini F, Coser A, Valsecchi S, Bonmassari R. Pacemaker therapy in very elderly patients: survival and prognostic parameters of single center experience. J Geriatr Cardiol. 2019 Dec;16(12):880-884. doi: 10.11909/j.issn.1671-5411.2019.12.010. PMID: 31911792; PMCID: PMC6938738.

10. Fumagalli S, Pieragnoli P, Haugaa KH, Potpara TS, Rasero L, Ramacciati N, Ricciardi G, Solimene F, Mascia G, Mascioli G, Zuo G, Roberts AT, Marchionni N, Lenarczyk R, Boveda S, Dagres N. The influence of age on the psychological profile of patients with cardiac implantable electronic devices: results from the Italian population in a multicenter study conducted by the European Heart Rhythm Association. Aging Clin Exp Res. 2019 Sep;31(9):1219-1226. doi: 10.1007/s40520-018-1088-5. Epub 2018 Dec 14. PMID: 30552563.

Reviewer 2 Report

Comments and Suggestions for Authors

This paper is extremely interesting , focusing on Pacemaker Optimization Mechanisms in the Spectrum of Cardiac Disease. Paper is well written, I have only one minor comment in order to improve the manuscript. Authors should  more focus and discuss about how the quality of life as well as older age should be both considered on pacemaker optimization mechanisms. s. The number of very elderly patients receiving pacemakers is increasing and little is known about survival in this specific subgroup, and strong risk factors for all-cause disease may also be non-cardiac. Please cite DOI: 10.1007/s40520-018-1088-5 ; and doi: 10.11909/j.issn.1671-5411.2019.12.010

Author Response

Response to reviewer 2

This paper is extremely interesting , focusing on Pacemaker Optimization Mechanisms in the Spectrum of Cardiac Disease. Paper is well written, I have only one minor comment in order to improve the manuscript. Authors should  more focus and discuss about how the quality of life as well as older age should be both considered on pacemaker optimization mechanisms. s. The number of very elderly patients receiving pacemakers is increasing and little is known about survival in this specific subgroup, and strong risk factors for all-cause disease may also be non-cardiac. Please cite DOI: 10.1007/s40520-018-1088-5 ; and doi: 10.11909/j.issn.1671-5411.2019.12.010

I have added a special section of age in cardiac spectrums along with references below

Age- Pacemakers are a frequent occurrence in the aged providing improved quality of life [9,10].  The aged have stiff blood vessels and when combined with orthostatic hypotension, the most important parameter to adjust is a higher heart rate

And in conclusion I added

Age and pacemakers are highly correlated.  The aged have special heart rate needs to prevent falls from orthostatic hypotension and fatigue due to reduced cardiac output. 

9. Marini M, Martin M, Saltori M, Quintarelli S, Zilio F, Guarracini F, Coser A, Valsecchi S, Bonmassari R. Pacemaker therapy in very elderly patients: survival and prognostic parameters of single center experience. J Geriatr Cardiol. 2019 Dec;16(12):880-884. doi: 10.11909/j.issn.1671-5411.2019.12.010. PMID: 31911792; PMCID: PMC6938738.

10. Fumagalli S, Pieragnoli P, Haugaa KH, Potpara TS, Rasero L, Ramacciati N, Ricciardi G, Solimene F, Mascia G, Mascioli G, Zuo G, Roberts AT, Marchionni N, Lenarczyk R, Boveda S, Dagres N. The influence of age on the psychological profile of patients with cardiac implantable electronic devices: results from the Italian population in a multicenter study conducted by the European Heart Rhythm Association. Aging Clin Exp Res. 2019 Sep;31(9):1219-1226. doi: 10.1007/s40520-018-1088-5. Epub 2018 Dec 14. PMID: 30552563.