What does this research mean for the field?

Dilated cardiomyopathy significantly increases myofibrillar calcium sensitivity of isometric tension compared to nonfailing donor hearts, a change likely mediated by reduced PKA-dependent phosphorylation of myofibrillar regulatory proteins. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

July 1, 1996Journal of Clinical InvestigationOpen Access

Myofibrillar calcium sensitivity of isometric tension is increased in human dilated cardiomyopathies: role of altered beta-adrenergically mediated protein phosphorylation.

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Dilated Cardiomyopathy (n=16). Intervention: Dilated cardiomyopathy (disease state) vs. Normal donor hearts. Primary outcome: Calcium sensitivity of isometric tension ([Ca2+]50 in µM) (p=<0.001).

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Key result

Dilated cardiomyopathy significantly increased myofibrillar calcium sensitivity of isometric tension compared to nonfailing donor hearts.

Population

Permeabilized myocyte-sized myofibrillar preparations from left ventricular biopsies of 9 patients with NYHA…

Comparison

In vitro treatment with the catalytic subunit of… vs Normal donor heart preparations and baseline…

Design

Preclinical

Authors

MWMathew R. WolffUniversity of Wisconsin–Madison SBS H BuckAlliance for Safe Kids SSScott W. StokerUniversity of Wisconsin–Madison

Discussion

Member takes

Implication

Should not yet alter DCM management; leaves open PKA modulation of myofilament sensitivity as a research target.

Study Design

Type

Observational (n=16)

Multicenter

Structured PICO

Population

Permeabilized myocyte-sized myofibrillar preparations (n=16) from left ventricular biopsies of 9 patients with NYHA Class III-IV dilated cardiomyopathy (DCM) undergoing cardiac transplantation or LVAD implantation, and preparations (n=10) from 6 normal donor hearts.

Intervention

In vitro treatment with the catalytic subunit of protein kinase A (PKA).

Comparator

Normal donor heart preparations and baseline (pre-PKA) state.

Outcome

Calcium sensitivity of isometric tension ([Ca2+]50).surrogate

Main Result

Absolute Event Rate: 2.46% vs 3.24%

p-value: p=<0.001

Increased myofibrillar calcium sensitivity in human dilated cardiomyopathy appears to be driven by reduced beta-adrenergically mediated (PKA-dependent) phosphorylation of regulatory proteins.

Limitations

Cardiomyopathic preparations were obtained from older and predominately male patients, while donor hearts were obtained from younger and predominately female patients.
Donor preparations were obtained from endomyocardial biopsies cardiopleged with University of Wisconsin solution, while failing preparations were transmural biopsies from beating hearts.
Brain death in donors may be associated with catecholamine release, potentially affecting physiologic conditions.
Myofibrillar mechanical function was examined at a single sarcomere length under steady state, isometric conditions.
Small sample size
Potential confounding by prior intravenous inotropic therapy in some patients
Low staining intensity of thin filament regulatory proteins limiting detection

Cite This Study

Wolff et al. (1996) conducted an observational in Dilated Cardiomyopathy (n=16). Dilated cardiomyopathy (disease state) vs. Normal donor hearts was evaluated on Calcium sensitivity of isometric tension ([Ca2+]50 in µM) (p=<0.001). Dilated cardiomyopathy significantly increased myofibrillar calcium sensitivity of isometric tension compared to nonfailing donor hearts.

synapsesocial.com/papers/6a18bbfdf58f28b4264aa428 https://doi.org/10.1172/jci118762

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Myofibrillar calcium sensitivity of isometric tension is increased in human dilated cardiomyopathies: role of altered beta-adrenergically mediated protein phosphorylation.

Discussion

Member takes

Implication

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Myofibrillar calcium sensitivity of isometric tension is increased in human dilated cardiomyopathies: role of altered beta-adrenergically mediated protein phosphorylation.

Discussion

Member takes

Implication

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

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