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Posts Tagged ‘Cheyne-Stokes Respiration’

Pre-operative Risk Factors and Clinical Outcomes Associated with Vasoplegia in Recipients of Orthotopic Heart Transplantation in the Contemporary Era.

Writer and Curator: Larry H. Bernstein, MD, FCAP

and

Curator: Aviva Lev-Ari, PhD, RN 

 

 Patarroyo M, Simbaqueba C, Shrestha K, Starling RC, Smedira N, Tang WH, Taylor DO.
 
BACKGROUND:  Patients who underwent orthotopic heart transplant (OHT) can develop vasoplegia, which is
  • associated with high mortality and morbidity.
Herein we examine the per-operative risk in OHT recipients at Cleveland Clinic.  Vasoplegic syndrome is
  • low systemic vascular resistance ( SVR index <1,600 dyn∙seg/cm5/m2 ) and
  • high cardiac output ( cardiac index >2.5 l/min/m2 )
  • within the first 4 postoperative hours.
VPS occurs more frequently after on pump CABG surgery versus off pump CABG surgery.

Methylene blue and vasoplegia: who, when, and how?

Stawicki SP, Sims C, Sarani B, Grossman MD, Gracias VH.
Department of Surgery, Division of Surgical Critical Care, University of Pennsylvania School of Medicine
Mini Rev Med Chem. 2008 May;8(5):472-90.  http://www.ncbi.nlm.nih.gov/pubmed/18473936
Vasoplegia or vasoplegic syndrome (VS) is thought to be due to
  • dysregulation of endothelial homeostasis and subsequent endothelial dysfunction
  • secondary to direct and indirect effects of multiple inflammatory mediators.
Vasoplegia has been observed in all age groups and in various clinical settings, such as anaphylaxis (including protamine reaction), sepsis, hemorrhagic shock, hemodialysis, and cardiac surgery. Among mechanisms thought to be contributory to VS, the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway appears to play a prominent role.
Methylene blue (MB),
  • an inhibitor of nitric oxide synthase (NOS) and guanylate cyclase (GC),
has been found to improve
  • the refractory hypotension associated with endothelial dysfunction of VS.
METHODS:  We reviewed peri-operative data from 311 consecutive adult patients who underwent OHT between January 2003 and June 2008.
Vasoplegia was defined as
  1. persistent low systemic vascular resistance,
  2. despite multiple intravenous pressor drugs at high dose,
  3. between 6 and 48 hours after surgery.
RESULTS:  In our cohort of 311 patients, 35 (11%) patients developed vasoplegia syndrome; these patients were more likely to be UNOS Status 1A, with
  • a higher body surface area (1.8 ± 0.25 vs 1.63 ± 0.36, p = 0.0007),
  • greater history of thyroid disease (38.2% vs 18.5%, p = 0.0075) and
  • a higher rate of previous cardiothoracic surgery (79% vs 48%, p = 0.0006).
Pre-operatively,
  • they were more frequently treated with aspirin (73% vs 48%, p = 0.005) and
  • mechanical assist devices (ventricular assist devices [VADs]: 45% vs 17%, p < 0.0001;
  • total artificial hearts: 8.6% vs 0%, p < 0.0001), and
  • less treated with milrinone (14.7% vs 45.8%, p = 0.0005).
Bypass time (118 ± 37 vs 142 ± 39 minutes, p = 0.0002) and
donor heart ischemic time (191 ± 46 vs 219 ± 51 minutes, p = 0.002) were longer, with
  • higher mortality (3.2% vs 17.1%, p = 0.0003) and morbidity in the first 30 days after transplant.
In the multivariate analysis, history of thyroid disease (odds ratio [OR] = 2.7, 95% CI 1.0 to 7.0, p = 0.04) and VAD prior to transplant (OR = 2.8, 95% CI 1.07 to 7.4, p = 0.03)
  • were independent risk factors for development of vasoplegia syndrome.
CONCLUSIONS:
  1. High body mass index,
  2. long cardiopulmonary bypass time,
  3. prior cardiothoracic surgery,
  4. mechanical support,
  5. use of aspirin, and
  6. thyroid disease
are risk factors associated with development of vasoplegia syndrome.

Other related articles fpublished on thie Open Access Online Sceintific Journal include the following:

Phrenic Nerve Stimulation in Patients with Cheyne-Stokes Respiration and Congestive Heart Failure (larryhbern)

http://pharmaceuticalintelligence.com/2013/06/20/phrenic-nerve-stimulation-in-patients-with-cheyne-stokes-respiration-and-congestive-heart-failure/
First drug to improve heart failure mortality in over a decade – HealthCanal.com (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/06/03/first-drug-to-improve-heart-failure-mortality-in-over-a-decade-healthcanal-com/
Meta-analysis: Heart Failure Worsens Short-term Prognosis of NSTE-ACS Patients – TCTMD
(Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/06/06/meta-analysis-heart-failure-worsens-short-term-prognosis-of-nste-acs-patients-tctmd/

Scientists prevent heart failure in mice (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/05/29/scientists-prevent-heart-failure-in-mice/
Economic Toll of Heart Failure in the US: Forecasting the Impact of Heart Failure in the United States – A Policy Statement From the American Heart Association (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/04/25/economic-toll-of-heart-failure-in-the-us-forecasting-the-impact-of-heart-failure-in-the-united-states-a-policy-statement-from-the-american-heart-association/
Stenosis, ischemia and heart failure (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/05/16/stenosis-ischemia-and-heart-failure/
Congestive Heart Failure & Personalized Medicine: Two-gene Test predicts response to Beta Blocker Bucindolol (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2012/10/17/chronic-heart-failure-personalized-medicine-two-gene-test-predicts-response-to-beta-blocker-bucindolol/

Gene Therapy Into Healthy Heart Muscle: Reprogramming Scar Tissue In Damaged Hearts
(Aviva Lev-Ari)

http://pharmaceuticalintelligence.com/2013/01/09/gene-therapy-into-healthy-heart-muscle-reprogramming-scar-tissue-in-damaged-hearts/

Heart Renewal by pre-existing Cardiomyocytes: Source of New Heart Cell Growth Discovered
Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2012/12/23/heart-renewal-by-pre-existing-cardiomyocytes-source-of-new-heart-cell-growth-discovered/

Heart Remodeling by Design – Implantable Synchronized Cardiac Assist Device: Abiomed’s Symphony (Aviva lev-Ari)

http://pharmaceuticalintelligence.com/2012/07/23/heart-remodeling-by-design-implantable-synchronized-cardiac-assist-device-abiomeds-symphony/

Survivals Comparison of Coronary Artery Bypass Graft (CABG) and Percutaneous Coronary Intervention (PCI) / Coronary Angioplasty (larryhbern)
http://pharmaceuticalintelligence.com/2013/06/23/comparison-of-cardiothoracic-bypass-and-percutaneous-interventional-catheterization-survivals/
First case in the US: Valve-in-Valve (Aortic and Mitral) Replacements with Transapical Transcatheter Implants – The Use of Transfemoral Devices (larryhbern)
http://pharmaceuticalintelligence.com/2013/06/23/valve-in-valve-replacements-with-transapical-transcatheter-implants/
Ventricular Assist Device (VAD): A Recommended Approach to the Treatment of Intractable Cardiogenic Shock (larryhbern)
http://pharmaceuticalintelligence.com/2013/06/18/a-recommended-approach-to-the-treatmnt-of-intractable-cardiogenic-shock/
Trans-apical Transcatheter Aortic Valve Replacement in a Patient with Severe and Complex Left Main Coronary Artery Disease (LMCAD) (larryhbern)
http://pharmaceuticalintelligence.com/2013/06/17/management-of-difficult-trans-apical-transcatheter-aortic-valve-replacement-in-a-patient-with-severe-and-complex-arterial-disease/
Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/06/03/clinical-indications-for-use-of-inhaled-nitric-oxide-ino-in-the-adult-patient-market-clinical-outcomes-after-use-therapy-demand-and-cost-of-care/

Space-filling model of the cyclic guanosine mo...

Space-filling model of the cyclic guanosine monophosphate molecule, also known as cGMP, a nucleotide. This image shows the anionic (negatively charged) form. Colour code (click to show) : Black: Carbon, C : White: Hydrogen, H : Red: Oxygen, O : Blue: Nitrogen, N : Orange: Phosphorus, P (Photo credit: Wikipedia)

Ball-and-stick model of the cyclic guanosine m...

Ball-and-stick model of the cyclic guanosine monophosphate molecule, also known as cGMP, a nucleotide. This image shows the anionic (negatively charged) form. Colour code (click to show) : Black: Carbon, C : White: Hydrogen, H : Red: Oxygen, O : Blue: Nitrogen, N : Orange: Phosphorus, P (Photo credit: Wikipedia)

English: Drawing showing targets of cGMP in cells

English: Drawing showing targets of cGMP in cells (Photo credit: Wikipedia)

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Heart Transplantation: NHLBI’s Ten year Strategic Research Plan to Achieving Evidence-based Outcomes

Writer and Curator: Larry H Bernstein, MD, FCAP

and

Curator: Aviva Lev-Ari, PhD, RN 

 

Heart transplantation research in the next decade–a goal to achieving evidence-based outcomes: National Heart, Lung, And Blood Institute Working Group.

Shah MR, Starling RC, Schwartz Longacre L, Mehra MR; Working Group Participants.

The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group (WG) on August 5 to 6, 2010 in Bethesda, Maryland to discuss future directions of research in heart transplantation (HT). The WG was composed of researchers with expertise in the basic science, clinical science, and epidemiological aspects of advanced heart failure and HT.
These experts were asked to
  1. identify the highest priority research gaps in the field and
  2. make recommendations for future research strategies.
The WG was also asked to include approaches that capitalize on current scientific opportunities and focus on areas that required unique NHLBI leadership. Finally, the WG was charged with developing recommendations that would have short- and long-term impact on the field of HT. The WG participants reviewed key areas in HT and identified the most urgent knowledge gaps.
These gaps were then organized into the following 4 specific research directions:
1) enhanced phenotypic characterization of the pre-transplant population;
2) donor-recipient optimization strategies;
3) individualized immunosuppression therapy; and,
4) investigations of immune and non-immune factors affecting late cardiac allograft outcomes.
Finally, because the HT population is relatively small compared with other patient groups, the WG strongly urged concerted efforts to enroll every transplant recipient into a clinical study and to increase collaborative networks to optimize research in this field.

Other  related articles published on this Open Access Online Scientific Journal, include the following:

Heart Failure Treatment Improves, But Death Rate Remains High : NPR (A Lev-Ari)
http://pharmaceuticalintelligence.com/2013/05/29/heart-failure-treatment-improves-but-death-rate-remains-high-npr/

The Heart: Vasculature Protection – A Concept-based Pharmacological Therapy including THYMOSIN (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/02/28/the-heart-vasculature-protection-a-concept-based-pharmacological-therapy-including-thymosin/

Resident-cell-based Therapy (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2012/04/30/93/

Amyloidosis with Cardiomyopathy (larryhbern)
http://pharmaceuticalintelligence.com/2013/03/31/amyloidosis-with-cardiomyopathy/

Blood-vessels-generating stem cells discovered (ritu.saxena)
http://pharmaceuticalintelligence.com/2012/10/22/blood-vessel-generating-stem-cells-discovered/

Stem Cell Research — The Frontier is at the Technion in Israel (A Lev-Ari)
http://pharmaceuticalintelligence.com/2012/09/06/stem-cell-research-the-frontier-is-at-the-technion-in-israel/

Phrenic Nerve Stimulation in Patients with Cheyne-Stokes Respiration and Congestive Heart Failure (larryhbern)
http://pharmaceuticalintelligence.com/2013/06/20/phrenic-nerve-stimulation-in-patients-with-cheyne-stokes-respiration-and-congestive-heart-failure/

First drug to improve heart failure mortality in over a decade – HealthCanal.com (A Lev-Ari)
http://pharmaceuticalintelligence.com/2013/06/03/first-drug-to-improve-heart-failure-mortality-in-over-a-decade-healthcanal-com/

Meta-analysis: Heart Failure Worsens Short-term Prognosis of NSTE-ACS Patients – TCTMD
(Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/06/06/meta-analysis-heart-failure-worsens-short-term-prognosis-of-nste-acs-patients-tctmd/

Scientists prevent heart failure in mice (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/05/29/scientists-prevent-heart-failure-in-mice/

Economic Toll of Heart Failure in the US: Forecasting the Impact of Heart Failure in the United States – A Policy Statement From the American Heart Association (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/04/25/economic-toll-of-heart-failure-in-the-us-forecasting-the-impact-of-heart-failure-in-the-united-states-a-policy-statement-from-the-american-heart-association/

Stenosis, ischemia and heart failure (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/05/16/stenosis-ischemia-and-heart-failure/

Congestive Heart Failure & Personalized Medicine: Two-gene Test predicts response to Beta Blocker Bucindolol (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2012/10/17/chronic-heart-failure-personalized-medicine-two-gene-test-predicts-response-to-beta-blocker-bucindolol/

Heart Renewal by pre-existing Cardiomyocytes: Source of New Heart Cell Growth Discovered
Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2012/12/23/heart-renewal-by-pre-existing-cardiomyocytes-source-of-new-heart-cell-growth-discovered/

Heart Remodeling by Design – Implantable Synchronized Cardiac Assist Device: Abiomed’s Symphony (A lev-Ari)
http://pharmaceuticalintelligence.com/2012/07/23/heart-remodeling-by-design-implantable-synchronized-cardiac-assist-device-abiomeds-symphony/

First case in the US: Valve-in-Valve (Aortic and Mitral) Replacements with Transapical Transcatheter Implants – The Use of Transfemoral Devices (larryhbern)
http://pharmaceuticalintelligence.com/2013/06/23/valve-in-valve-replacements-with-transapical-transcatheter-implants/
Ventricular Assist Device (VAD): A Recommended Approach to the Treatment of Intractable

Cardiogenic Shock (larryhbern)
http://pharmaceuticalintelligence.com/2013/06/18/a-recommended-approach-to-the-treatmnt-of-intractable-cardiogenic-shock/

Trans-apical Transcatheter Aortic Valve Replacement in a Patient with Severe and Complex Left Main Coronary Artery Disease (LMCAD) (larryhbern)
http://pharmaceuticalintelligence.com/2013/06/17/management-of-difficult-trans-apical-transcatheter-aortic-valve-replacement-in-a-patient-with-severe-and-complex-arterial-disease/

Forrester-classification for classification of...

Forrester-classification for classification of Congestive heart failure ; Forrester-Klassifikation zur Einteilung einer akuten Herzinsuffizienz (Photo credit: Wikipedia)

Artificial heart: JARVIK-7 Heart, provided to ...

Artificial heart: JARVIK-7 Heart, provided to the National Heart, Lung and Blood Institute (NHLBI) by the University of Utah. (Photo credit: Wikipedia)

Schematic of a transplanted heart with native ...

Schematic of a transplanted heart with native lungs and the great vessels. (Photo credit: Wikipedia)

English: Ventricular assist device

English: Ventricular assist device (Photo credit: Wikipedia)

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Phrenic Nerve Stimulation in Patients with Cheyne-Stokes Respiration and Congestive Heart Failure

Writer: Larry H Bernstein, MD, FCAP

and

Curator: Aviva Lev-Ari, PhD, RN

Transvenous Phrenic Nerve Stimulation in Patients With Cheyne-Stokes Respiration and Congestive Heart Failure:A Safety and Proof-of-Concept Study

Xi-Long Zhang, MD; Ning Ding; Hong Wang; Ralph Augostini; Bing Yang; Di Xu; Weizhu Ju; Xiaofeng Hou; Xinli Li; Buqing Ni, PhD; Kejiang Cao; Isaac George; Jie Wang, MD, PhD; Shi-Jiang Zhang
Chest. 2012; 142(4):927-934. doi:10.1378/chest.11-1899
Text Size: A A A

Background:  Cheyne-Stokes respiration (CSR), which often occurs in patients with congestive heart failure (CHF), may be a predictor for poor outcome. Phrenic nerve stimulation (PNS) may interrupt CSR in patients with CHF. We report the clinical use of transvenous PNS in patients with CHF and CSR.

Methods:  Nineteen patients with CHF and CSR were enrolled. A single stimulation lead was placed at the junction between the superior vena cava and brachiocephalic vein or in the left-side pericardiophrenic vein. PNS stimulation was performed using Eupnea System device (RespiCardia Inc). Respiratory properties were assessed before and during PNS. PNS was assessed at a maximum of 10 mA.

Results:  Successful stimulation capture was achieved in 16 patients. Failure to capture occurred in three patients because of dislocation of leads. No adverse events were seen under maximum normal stimulation parameters for an overnight study. When PNS was applied following a series of central sleep apneic events, a trend toward stabilization of breathing and heart rate as well as improvement in oxygen saturation was seen. Compared with pre-PNS, during PNS there was a significant decrease in apnea-hypopnea index (33.8 ± 9.3 vs 8.1 ± 2.3, P = .00), an increase in mean and minimal oxygen saturation as measured by pulse oximetry (89.7% ± 1.6% vs 94.3% ± 0.9% and 80.3% ± 3.7% vs 88.5% ± 3.3%, respectively, all P = .00) and end-tidal CO2 (38.0 ± 4.3 mm Hg vs 40.3 ± 3.1 mm Hg, P = .02), but no significant difference in sleep efficiency (74.6% ± 4.1% vs 73.7% ± 5.4%, P = .36).

Conclusions:  The preliminary results showed that in a small group of patients with CHF and CSR, 1 night of unilateral transvenous PNS improved indices of CSR and was not associated with adverse events.

Trial registry:  ClinicalTrials.gov; No.: NCT00909259; URL: www.clinicaltrials.gov

http://journal.publications.chestnet.org/article.aspx?articleid=1215995

Transvenous phrenic nerve stimulation in patients with Cheyne-Stokes respiration and congestive heart failure: a safety and proof-of-concept study

Zhang Xi-Long; Ding N, Wang H, Augostini R, Yang B.
CHEST 2012; 142(4):927–934
Trial registry: ClinicalTrials.gov; No.: NCT00909259; URL: http://www.clinicaltrials.gov
http://dx.doi.org/10.1378/chest.11-1899

Introduction

Cheyne-Stokes respiration (CSR), a condition characterized by a cyclic pattern of waxing and waning ventilation interposed by central apneas or hypopneas, may affect up to 40% of patients with congestive heart failure (CHF).  Whether CSR is related to significantly increased morbidity and mortality 2 or has no impact on long-term survival in patients with CHF is controversial. Nevertheless, several investigators have reported that CSR might be an independent prognostic index of poor outcome in patients with CHF, so that Cheyne-Stokes respiration (CSR), which often occurs in patients with congestive heart failure (CHF), may be a predictor for poor outcome. CSR in patients with CHF is believed to be associated with a hypersensitivity to arterial CO 2 during sleep. The key pathophysiologic mechanism leading to all forms of periodic breathing is the oscillation of blood CO 2 level below and above the apneic threshold.  Clinically, these pathophysiologic changes may translate to sleep fragmentation, excessive daytime sleepiness, reduced exercise capacity, and, possibly, ventricular arrhythmias.
Current treatment options for CSR include medications, positive airway pressure devices such as adapt servo-ventilation, or oxygen therapy. Although all these therapies have shown benefi t in some patients, none has shown a consistent benefi t of suffi cient clinical magnitude to reduce mortality and morbidity. In the current study, we explored the initial feasibility, safety, and possible effects of unilateral, transvenous, synchronized PNS on CSR in 19 patients with CHF . This novel treatment resulted in a marked reduction of minute ventilation and possible improvement of CSR. The authors here suggest that phrenic nerve stimulation (PNS) may interrupt CSR in patients with CHF.

Study Population

 Nineteen patients with CHF and CSR were enrolled.  All study patients (N 5 19) had received a diagnosis of CSR and chronic CHF and were hospitalized in The First Affiliated Hospital of Nanjing Medical University (Nanjing, China). Of them, 12 with rheumatic cardiac valve disease were waiting forcardiac surgery, and seven (fi ve with dilated cardiomyopathy and two with hypertensive heart disease) were enrolled from the cardiology ward because of severe heart failure.
The inclusion criteria were aimed at identifying patients with symptoms or a diagnosed condition indicative of CSR who would tolerate the testing procedure. The patients continued on their standard medical regimen during participation, and in the case of an adverse event, medical treatment was at the discretion of the investigator. The inclusion criteria were as follows: (1) both patient and direct family member willingness to sign a Patient Ethics Committee-approved informed consent, (2) age > 18 years, (3) index CSR of > 15 times/h, (4) history of CHF with a left ventricle ejection fraction < 45%, and (5) ability to tolerate the study procedure and remain clinically stable for the duration of the study. Exclusion criteria were as follows: (1) baseline oxygen saturation <  90% on a stable FiO2 ; (2) evidence of phrenic nerve palsy; (3) temperature > 38.0°C; (4) inability to place stimulation lead (eg, coagulopathy, distorted anatomy, etc); (5) current enrollment in another clinical study that may confound the results of the present study; (6) no informed consent; (7) pregnancy or of childbearing potential without a negative pregnancy test within 10 days of the study procedure; (8) pacemaker, implantable cardioverter defibrillator, or cardiac resynchronization device; (9) severe COPD; (10) a history of myocardial infarction within 6 months prior to the study; and (11) unstable angina.

Study Design

 This short-term, prospective, open-label, nonrandomized feasibility study consisted of a treatment-only cohort in which each patient served as his or her own control. After patients were screened and enrolled in the study, PNS leads were placed through an interventional procedure for observation of 1 night only. During the 1-night study, we examined whether PNS caused pain, arousal during sleep, arrhythmia, changes in BP, and changes in either normal breathing or sleep apnea. We also examined the impact of PNS on central, obstructive, and mixed sleep apnea. Alterations in sleep apnea and hypopnea events were compared before and during PNS. “Before stimulation” was defined as the number of sleep apnea and hypopnea events occurring during a segment of 10 min just before delivery of PNS and served as the control for the effects of PNS. The total number of the 10-min segments before PNS, the total number of sleep apnea and hypopnea events occurred during the sum of the 10-min time were calculated,  then averaged (total number of sleep apnea and hypopnea events/total hours of the 10-min segments from all patients) and presented as the apnea-hypopnea index (AHI) for statistical analysis. AHI during PNS were also calculated and compared with AHI prior to PNS.

Sleep Study and Monitored Parameters

 All participants underwent a nocturnal, in-laboratory polysomnography (Embla S4500 PSG Amplifi er; Natus Medical Inc) and were monitored for at least 7 h overnight. The standard polysomnography recorded the EEG, bilateral electrooculograms, submental  electromyogram, ECG, chest and abdominal movement using respiratory effort bands, body position, nasal airflow using a pressure sensor, and oxygen saturation as measured by pulse oximetry (Sp o 2 ).
EEG, sleep staging, and arousals were monitored and scored using 30 epochs according to the method of Rechtschaffen and Kales. Classification of apnea and hypopnea was described by standard methodologies. CSR was identified as a special kind of CSA behaving as a cyclic pattern of periods of hyperventilation with waxing and waning tidal volumes alternating with periods of central hypopnea/apnea .

Lead Placement and PNS

A single stimulation lead was placed at the junction between the superior vena cava and brachiocephalic vein or in the left-side pericardiophrenic vein. PNS stimulation was performed using Eupnea System device (RespiCardia Inc). Respiratory properties were assessed before and during PNS. PNS was assessed at a maximum of 10 mA.

Results

Successful stimulation capture was achieved in 16 patients. Failure to capture occurred in three patients because of dislocation of leads. No adverse events were seen under maximum normal stimulation parameters for an overnight study.  No new arrhythmias, muscle contractions, arterial BP variations, pain, or unpleasant sensations were observed once PNS was delivered during sleep for these patients. It was confirmed that the catheter could be secured adequately to obtain consistent predictable stimulation thresholds without arousal from sleep. During occurrence of CSR, intermittent PNS signals were first confirmed to be successfully captured in 16 patients. When PNS was applied following a series of central sleep apneic events, a trend toward stabilization of breathing and heart rate.  An improvement in oxygen saturation and elevation of end-tidal CO2 was observed as longer continuous stimulation was performed. The period of stable breathing lasted as long as 10 to 20 min in some patients after stimulation.  They found that when electric connection to the nerve was consistent, stimulation resulted in a reduced hyperventilation followed by the reduction or elimination of CSR.
Compared with pre-PNS, during PNS there was a significant decrease in apnea-hypopnea index (33.8 ± 9.3 vs 8.1 ± 2.3, P = .00), an increase in mean and minimal oxygen saturation as measured by pulse oximetry (89.7% ± 1.6% vs 94.3% ± 0.9% and 80.3% ± 3.7% vs 88.5% ± 3.3%, respectively, all P = .00) and end-tidal CO2 (38.0 ± 4.3 mm Hg vs 40.3 ± 3.1 mm Hg, P = .02), but no significant difference in sleep efficiency (74.6% ± 4.1% vs 73.7% ± 5.4%, P = .36).

Discussion

CSR is characterized by cyclical oscillations of respiration and apnea. The incidence of CSR ranges from 10% to 20% in patients with stable CHF and up to 40% to 50% of all patients with New York Heart Association functional class III?IV CHF.  Nocturnal breathing alterations in patients with CHF are believed to be due to hypersensitivity to CO 2 during sleep. Breathing is controlled by a negative feedback system in which an increase in Pa co 2 stimulates breathing, whereas a decrease in Pa co 2 inhibits breathing. Normally, Pa co 2 is maintained within a narrow range. Patients with CHF and CSA have a more brisk ventilatory response to CO 2 than those without CSA.
The preliminary results showed that in a small group of patients with CHF and CSR, 1 night of unilateral transvenous PNS improved indices of CSR and was not associated with adverse events.
The study was performed using temporary catheters or leads in the right-side brachiocephalic vein, SVC, or left-side pericardiophrenic vein to transvenously stimulate the hemidiaphragm through either the leftside or the right-side phrenic nerve. To consistently stimulate the phrenic nerve using acceptable and safe current levels ( < 10 mA), the stimulation electrode needs to be within 2 to 5 mm from the phrenic nerve.  This type of stimulation caused significantly improved respiratory parameters in patients with CHF and further support that oscillation of CO 2 level in the blood below and above the apneic threshold is a central mechanism leading to the CSR pattern of breathing. Stabilization of CO 2 levels through PNS produced a regular breathing pattern, improvement in oxygen saturation, and fewer apneic events.
Dr.  Isaac George: contributed to data evaluation and drafting of the manuscript.

Related articles

Other related articles published on this Open Access Online Scientific Journal include the following:

Implantable Synchronized Cardiac Assist Device Designed for Heart Remodeling: Abiomed’s Symphony

Aviva Lev-Ari, PhD, RN, 7/11/2012

http://pharmaceuticalintelligence.com/2012/07/11/implantable-synchronized-cardiac-assist-device-designed-for-heart-remodeling-abiomeds-symphony/

Biomaterials Technology: Models of Tissue Engineering for Reperfusion and Implantable Devices for Revascularization

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/5_04_2013/bernstein_lev-ari/Bioengineering_of_Vascular_and_Tissue_Models

Foreseen changes in Guideline of Treatment of Cardiogenic Shock with Intra-aortic Balloon counterPulsation (IABP)

Evidence for Overturning the Guidelines in Cardiogenic Shock

Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care

Aviva Lev-Ari, PhD, RN, 6/3/2013

Aviral Vatsa PhD MBBS, 1/4/2013

Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination?

Aviva Lev-Ari, PhD, RN, 10/19/2013

http://pharmaceuticalintelligence.com/2012/10/19/clinical-trials-results-for-endothelin-system-pathophysiological-role-in-chronic-heart-failure-acute-coronary-syndromes-and-mi-marker-of-disease-severity-or-genetic-determination/

Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems

Justin Pearlman MD ME PhD MA FACC, Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/05/15/diagnosis-of-cardiovascular-disease-treatment-and-prevention-current-predicted-cost-of-care-and-the-promise-of-individualized-medicine-using-clinical-decision-support-systems-2/

Visualisation of Cheyne-Stokes respiration

Visualisation of Cheyne-Stokes respiration (Photo credit: Wikipedia)

Cheyne-Stokes respiration

Cheyne-Stokes respiration (Photo credit: Wikipedia)

Cheyne-Stokes respiration

Cheyne-Stokes respiration (Photo credit: Wikipedia)

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