Prognostic impact of vasopressor test in transcatheter edge-to-edge repair of secondary mitral regurgitation: The PETIT study.

BACKGROUND: Vasopressor test (VPT) might be useful in patients with functional mitral regurgitation (MR) and left ventricular dysfunction (MITRA-FR-like patients) during transcatheter edge-to-edge repair (TEER). AIMS: We aimed to evaluate the prognostic impact of VPT. METHODS: MR treated with TEER were included in a multicenter prospective registry. VPT was used intraprocedurally in patients with left ventricular dysfunction and/or hypotension. The 1-year echocardiographic and clinical outcomes were compared according to the use of VPT. The primary endpoint was a combination of mortality + heart failure (HF) readmission at 1-year. RESULTS: A total of 1115 patients were included, mean age was 72.8 ± 10.5 years and 30.4% were women. VPT was performed in 128 subjects (11.5%), more often in critically ill patients with biventricular dysfunction. Postprocedurally the VPT group had greater rate of MR ≥ 2+ (46.9% vs. 31.7%, p = 0.003) despite greater number of devices (≥2 clips, 52% vs. 40.6 p = 0.008) and device repositioning or new clip in 12.5%. At 1-year, the primary endpoint occurred more often in the VPT group (27.3% vs. 16.9%, p = 0.002) as well as all-cause mortality (21.9% vs. 8.1%, p ≤ 0.001) but no differences existed in HF readmission rate (14.8% vs. 13.2%, p = 0.610), cardiovascular mortality (4.4% vs. 3.9%, p = 0.713) or residual MR ≥ 2+ (51.1% vs 51.7%, p = 0.371). CONCLUSIONS: Dynamic evaluation of MR during TEER procedure through VPT was performed in patients with worse baseline risk who also presented higher all-cause mortality at 1-year follow-up. However, 1-year residual MR, cardiovascular mortality and HF readmission rate remained comparable suggesting that VPT might help in the management of MITRA-FR-like patients.

Bicaval TricValve Implantation in Patients With Severe Symptomatic Tricuspid Regurgitation: 1-Year Follow-Up Outcomes.

BACKGROUND: Several orthotopic transcatheter strategies have been developed to treat severe tricuspid regurgitation (TR); however, many patients are deemed unsuitable. Caval valve implantation with the TricValve system addresses this unmet need. OBJECTIVES: This study sought to determine the impact of TricValve on systemic congestion and quality of life (QOL) at 1 year. METHODS: The TRICUS (Safety and Efficacy of the TricValve® Transcatheter Bicaval Valves System in the Superior and Inferior Vena Cava in Patients With Severe Tricuspid Regurgitation) and TRICUS EURO studies were prospective, nonblinded, nonrandomized, single-arm trials representing the early-in-man experience of the TricValve system in NYHA functional class III or IV severe TR patients, optimally medicated and ineligible for open heart surgery, with significant caval backflow. The primary endpoint was QOL metrics and functional status. The 1-year results of the combined cohort are described here. RESULTS: Forty-four patients were included. Mean age was 76.2 ± 7.5 years, 81.0% were women, and the TRISCORE (risk score model for isolated tricuspid valve surgery) was 5.3 ± 1.3. Clinical improvement at 1 year was achieved in 42 (95.5%) patients, measured by (at least 1 of) an increase in ≥15 points from baseline in 12-item Kansas City Cardiomyopathy Questionnaire score, improvement to NYHA functional class to I or II, or an increase ≥40 m in the 6-minute walk test. There were 3 (6.8%) deaths at 1-year follow-up (1 cardiovascular), and the heart failure rehospitalization rate was 29.5%. Stent fracture, conduction system disturbances, or clinically significant leaflet thrombosis were not detected. Abolished hepatic vein backflow was achieved and persisted in 63.8% of the patients, contributing towards a reduction in congestive symptoms, N-terminal pro-B-type natriuretic peptide levels (P = 0.032), and diuretic treatment. CONCLUSIONS: Caval valve implantation with the TricValve system associated with meaningful 1-year clinical improvements in terms of QOL along with relatively low mortality rates. (TRICUS Study - Safety and Efficacy of the TricValve® Device; NCT03723239).

Clinical outcomes of TAVI with the Myval balloon-expandable valve for non-calcified aortic regurgitation.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) in non-calcified aortic regurgitation (NCAR) is an off-label procedure. The balloon-expandable Myval includes extra-large sizes (30.5 mm and 32 mm) of interest in this setting. AIMS: We aimed to evaluate the safety and feasibility of Myval in NCAR. METHODS: This was an international, multicentre, observational study that enrolled all consecutive patients with symptomatic severe NCAR undergoing TAVR with the Myval device. The images were centrally analysed. RESULTS: A total of 113 patients were recruited, 64.6% were men, the mean age was 78.4±7.5 years, and the Society of Thoracic Surgeons score was 2.7±1.7%. Aortic root dilatation was present in 59.3% of patients, 7.1% were bicuspid, and the mean annular area was 638.6±106.0 mm2. The annular area was beyond the recommended range for extra-large sizes in 2.6% of cases, and additional volume was added in 92% (median 4 cc, up to 9 cc). The extra-large sizes were used in 95 patients (84.1%), and the mean oversizing was 17.9±11.0%. The technical success rate was 94.7%; the rate of residual ≥moderate aortic regurgitation was 8.9%, and the pacemaker rate was 22.2%. There were no cases of annular rupture, cardiac tamponade, or aortic dissection, but in 4 patients (3.5%) valve embolisation occurred (1 antegrade and 3 ventricular), all in cases with a tapered left ventricle outflow tract (p=0.007). Thirty-day and 1-year mortality were 5.3% and 9.7%, respectively. Technical success was associated with better survival (97.1% vs 72.7%; p=0.012), and valve embolisation was the main determinant of mortality (p=0.047). CONCLUSIONS: Myval is a feasible and safe option for selected non-operable patients with NCAR and demonstrated good midterm outcomes and lack of impact of oversizing on device durability.

Capacity and quality of maternal and child health services delivery at the subnational primary healthcare level in relation to intermediate health outputs: a cross-sectional study of 12 low-income and middle-income countries.

OBJECTIVES: To examine the capacity and quality of maternal and child health (MCH) services at the subnational primary healthcare (PHC) level in 12 low-income and middle-income countries (LMICs) and its association with intermediate health outputs such as coverage and access to care. DESIGN: Observational cross-sectional study using matched subnational data from service provision assessment surveys and demographic health surveys from 2007 to 2019. SETTINGS: 138 subnational areas with available survey data in 12 LMICs (Afghanistan, Bangladesh, Democratic Republic of Congo, Haiti, Kenya, Malawi, Namibia, Nepal, Rwanda, Senegal, Tanzania and Uganda). OUTCOMES: Eight intermediate MCH outcomes/outputs were explored: (1) met need for family planning by modern methods; (2) attendance of four or more antenatal care visits; (3) perceived financial barriers to care; (4) perceived geographical barriers to care; (5) diphtheria-pertussis-tetanus (DPT) third dose coverage; (6) DPT dropout-rate; (7) care-seeking for pneumonia; and (8) oral rehydration solutions coverage. RESULTS: Overall, moderate-to-poor PHC performance was observed across the 12 countries, with substantial heterogeneity between the different subnational areas in the same country as well as within the same subnational area across both capacity and quality subdomains. The analysis of the relationship between PHC service delivery and child health outcomes revealed that recent supervision (b=0.34, p<0.01) and supervisors' feedback (b=0.28, p<0.05) were each associated with increased care-seeking for pneumonia. We also observed the associations of several measures of capacity and quality with DPT immunisation. The analysis of maternal health outcomes yielded only a few statistically significant results at p<0.05 level, however, none remained significant after adjusting for other covariates. CONCLUSION: The results of this analysis illustrate the heterogeneity in the capacity and quality of PHC service delivery within LMICs. Countries seeking to strengthen their PHC systems could improve PHC monitoring at the subnational level to better understand subnational bottlenecks in service delivery.

Transcatheter Mitral Valve-in-Valve Implantation with the Balloon-Expandable Myval Device.

Background: The vast majority of transcatheter valve-in-valve (ViV) mitral procedures have been reported with the SAPIEN family. We aimed to report the preliminary experience with the Myval balloon-expandable device in this setting. Methods: Multicenter retrospective study of high-risk surgical patients with mitral bioprosthesis degeneration undergoing transcatheter ViV implantation with Myval device. Results: A total of 11 patients from five institutions were gathered between 2019 and 2022 (age 68 ± 7.8, 63% women). The peak and mean transvalvular gradients were 27 ± 5 mmHg and 14.7 ± 2.3 mmHg, respectively, and the predicted neo-left ventricular outflow tract (neo-LVOT) area was 183.4 ± 56 mm2 (range: 171 to 221 mm2). The procedures were performed via transfemoral access in all cases (through echocardiography-guided transeptal puncture (81.8% transesophageal, 11.2% intracardiac)). Technical success was achieved in all cases, with no significant residual mitral stenosis in any of them (peak 7.2 ± 2.7 and mean gradient 3.4 ± 1.7 mmHg) and no complications during the procedure. There were no data of LVOT obstruction, migration, or paravalvular leak in any case. Mean hospital stay was 3 days, with one major vascular complication and no stroke. At 6-month follow-up, there was one case with suboptimal anticoagulation presenting an increase in the transmitral gradients (mean 15 mmHg) that normalized after optimization of the anticoagulation, but no other relevant events. Conclusions: Transseptal ViV mitral implantation with the balloon-expandable Myval device was feasible and safe avoiding redo surgery in high-risk patients with bioprosthesis degeneration.

El papel del óxido nítrico en la modulación del proceso inflamatorio de la enfermedad periodontal / The role of nitric oxide in the modulation of inflammatory periodontal disease

El óxido nítrico (NO) es un radical libre que participa de prácticamente todos los procesos fisiológicos del organismo; sin embargo, en grandes concentraciones puede actuar de forma perjudicial en los tejidos. Su acción inmuno-regulatoria está presente en la inflamación y en los mecanismos de auto inmunidad, siendo intensamente estudiada en el área médica. Recientemente, algunos estudios también han citado al NO como factor etiopatogénico de la enfermedad periodontal, el cual posee naturaleza inflamatoria y multifactorial. La acción del NO depende de su concentración en el organismo, pudiendo ser benéfica o perjudicial y, basada en eso, investigaciones han enfocado el efecto de algunos inhibidores de NO como supuestos agentes terapéuticos en los procesos inflamatorios. A partir de ese contexto, este trabajo tuvo como objetivo relatar el papel del NO y de la inhibición de la óxido nítrico sintasa (NOS) en el proceso de la modulación de la enfermedad periodontal. En conclusión, se puede sugerir que el NO parece ejercer un papel fundamental en la evolución de la enfermedad periodontal inflamatoria y, que la inhibición de la NOS puede ser considerada una terapéutica promisora en la modulación del proceso

Nitric oxide (NO) is a free radical with participation in almost all physiologic host processes; however, in high concentrations it may damage the tissues. Its immunoregulatory action is present in the inflammation and in auto-immune mechanisms, being intensively studied in the medical area. Recently, some studies have also reported that NO could play a role as etiopathogenic factor of the periodontal disease, which shows inflammatory and multifactorial course. Due to beneficial or damage effects of NO, according to its concentrations, some studies have been focused in the evaluation of inhibitor of NO-Synthase (NOS) as therapeutic agents in inflammatory processes. In this context, the aim of this study was to report the role of NO and NOS inhibition in the periodontal disease modulation process. In conclusion, it could be suggested that NO seems to play an essential role in evolution of inflammatory periodontal disease, and that the NOS inhibition may be considered as a promising therapeutic in modulation of inflammatory process

Comparative assessment of the flow rate of root canal sealers / Estudo comparativo do escoamento de cimentos obturadores endodônticos

Purpose: This study evaluated the flow rate of the Acroseal, AH Plus, Endomethasone N, Sealapex, and ActiV GP according to the standards of the ISO specification 6876/2001. Methods: A volume of 0.05 mL of the cement mixed according to the manufacturer's recommendations was placed on a glass plate. At 180±5 s after the commencement of mixing, the second glass plate was placed on top of the sealer, followed by the weight of mass approximately 100 g to make a total mass on the plate of 120±2 g. Ten min after the start of mixing, the weight was removed and the value of the diameter of the compressed disc of sealer was measured. The mean of three such determinations for each sealer was taken as the flow of the material. The mean values were compared using ANOVA and Tukey's tests. Results: The results obtained were: Acroseal 21.24 mm, AH Plus 22.72 mm, ActiV GP 24.90 mm, Endomethasone N 18.76 mm, and Sealapex 25.15 mm. Conclusion: Only the Endomethasone N did not conform to ISO Specification that requires that a sealer shall have a diameter of not less than 20 mm. The Sealapex achieved the greatest flow, but it did not differ from Activ GP and AH Plus (P>0.5).

Objetivo: Este estudo avaliou o escoamento do Acroseal, AH Plus, Endomethasone N, Sealapex e ActiV GP de acordo com a especificação ISO 6876/2001. Metodologia: Um volume de 0,05 mL do cimento manipulado de acordo com as recomendações do fabricante foi colocado numa placa de vidro. Aos 180±5 s após o início da espatulação, uma segunda placa de vidro foi colocada sobre o cimento, seguida por um peso de massa de 100 g para fazer um total de 120±2 g. Dez minutos após o começo da manipulação o peso foi removido e o valor do diâmetro do disco de cimento foi mensurado. A média de 3 mensurações para cada cimento foi tomada como o escoamento do material. Os dados foram comparados estatisticamente pelos testes ANOVA e Tukey. Resultados: Os escoamentos obtidos foram: Acroseal 21.,4 mm, AH Plus 22,72 mm, ActiV GP 24,90 mm, Endomethasone N 18,76 mm e Sealapex 25,15 mm. Conclusão: Apenas o Endomethasone N não se enquadrou na especificação ISO a qual requer que o cimento tenha um diâmetro não inferior a 20 mm. O Sealapex alcançou o melhor escoamento, mas não foi estatisticamente diferente do Activ GP e AH Plus (P>0,05).

Directrices para el diagnóstico de la diabetes mellitus y la conducta clínica periodontal

La medicina periodontal es un área de importancia actual por relacionar enfermedades sistémicas a patologías periodontales. Se han realizado estudios con el propósito de verificar esta relación, y por eso, la literatura viene enfocando a la cavidad bucal como un importante instrumento en el diagnóstico precoz de patologías sistémicas, como en el caso de la diabetes mellitus. Para poder sospechar de un cuadro diabético, los odontólogos deben observar manifestaciones clínicas como abscesos periodontales recurrentes, necrosis de la encía marginal y aumento de la predisposición a infecciones. Una vez observadas estas condiciones, el odontólogo deberá solicitar los exámenes necesarios para el diagnóstico de la diabetes y entonces encaminar al paciente para su tratamiento médico. Considerando la importancia del diagnóstico precoz nos propusimos en el presente artículo revisar los estudios que investigan esta posible correlación, buscando presentar las principales alteraciones clínicas y sistémicas de los pacientes portadores de esas patologías, para mejor esclarecer a los profesionales clínicos de cómo proceder en relación al control metabólico de los pacientes (exámenes de sangre) y que conducta clínica es la más adecuada.

The periodontal medicine is an area that has been receiving importance, due the association between periodontal diseases and systemic conditions. Studies have been conducted in order to verify this relationship, and that is why literature has been focusing on the oral cavity as an important tool in the early diagnosis of systemic diseases, such as diabetes mellitus. Then the literature have been focused the oral cavity which an important instrument of early diagnosis about some systemic pathologies such as diabetes mellitus. In front of the suspect of diabetes conditions, many oral healthy complications have been observed by health care that include recurrent periodontal abscess, gingival marginal necrosis and high susceptibility to infections. Once these conditions were observed, the surgeon dentist should request the necessary exams for the diagnosis of the diabetes and then to direct the patient for medical treatment. In front of such considerations, we set out in this article to review studies that investigated the possible correlation, seeking to present major alterations clinics and systemic patients with these diseases, to better clarify the clinical practitioners on how to proceed in relation to metabolic control of patients (blood tests) and clinical behavior is the most appropriate.

Efectividad de las técnicas rotatoria y oscilatoria en la preparación de conductos radiculares de conformación ovalada / Efetividade das técnicas rotatória e oscilatória no preparo biomecânico de canais radiculares de conformação ovalada / Effectiveness of root canal rotary and oscillatory peraparation techniques in flattened root canals

Este trabajo evaluó la preparación biomecánica de conductos radiculares de conformación ovalada, en cuanto al área de utilización de los instrumentos, se aplicaron cuatro técnicas: instrumentación oscilatoria con instrumentos de acero inoxidable Endo-Eze; instrumentación rotatoria con instrumentos de níquel-titanio del sistema Profile, instrumentación oscilatoria utilizando o sistema Profile, e instrumentación rotatoria con sistema Profile asociada a la instrumentación oscilatoria con sistema Endo-Eze. Fueron utilizadas 40 raíces distales de molares inferiores extraídos. Los especimenes fueron incluidos en resina poliéster cristal incolora, obteniendo un bloque con marcas en la porción externa. La raíz incluida en el bloque de resina fue seccionada de forma que pudiéramos visualizar la porción media del conducto radicular. Los dos cortes del bloque de resina fueron reposicionados, posibilitando la instrumentación de los conductos radiculares. Las imágenes de la superficie inferior de la sección media de cada raíz fueron obtenidas a través de una cámara digital y las imágenes archivadas. Después de la instrumentación, fueron realizadas nuevas fotografías. Las imágenes fueron transferidas para el programa AutoCAD, para que los conductos radiculares fueran trazados y la medición de las áreas de actuación de los instrumentos fuera realizada. Los resultados demostraron que no hubo diferencia estadísticamente significativa entre los grupos, aún haya sido observado un desgaste más uniforme en las paredes dentinarias por la instrumentación con los sistemas Profile y Endo-Eze asociados

This study evaluated the biomechanical preparation of flattened root canals, considering the effective area of instrumentation, using four different techniques: oscillatory instrumentation using Endo-Eze instruments; rotary instrumentation using Profile system; oscillatory instrumentation using Profile system; and rotary instrumentation with Profile system associated to oscillatory instrumentation with Endo-Eze system. A total of 40 distal roots of lower molars were used. These teeth were included in transparent resin blocks and grooves were made in the external portion of the block. The resin block containing the teeth was cut showing the median third of the root. Using a digital camera, the lower portion from the median third of the root were photographed, and the images recorded. After instrumentation, new images were obtained. The images were transferred to AutoCAD, the root canal was demarcated and the root canal area was measured. The results showed no statistically significant difference between the groups. However, a more uniform enlargement was observed in the group where oscillatory and rotary instrumentation were associated

Este trabalho avaliou o preparo biomecânico de canais radiculares de conformação ovalada, quanto à área de atuação dos instrumentos, utilizando quatro técnicas: instrumentação oscilatória com instrumentos de aço inoxidável Endo-Eze; instrumentação rotatória com instrumentos de níquel-titânio do sistema Profile, instrumentação oscilatória utilizando o sistema Profile, e instrumentação rotatória com sistema Profile associada à instrumentação oscilatória com sistema Endo-Eze. Foram utilizadas 40 raízes distais de molares inferiores extraídos. Os espécimes foram incluídos em resina poliéster cristal incolor, obtendo-se um bloco com marcas na porção externa. A raiz incluída no bloco de reina foi seccionada de forma a visualizarmos a porção média do canal radicular. Os dois cortes do bloco de resina foram reposicionados, possibilitando a instrumentação dos canais radiculares. As imagens da superfície inferior da secção média de cada raiz foram obtidas através de uma câmera digital e as imagens arquivadas. Após a instrumentação, foram realizadas novas fotografias. As imagens foram transferidas para o programa AutoCAD, para q os canais radiculares fossem traçados e a mensuração das áreas de atuação dos instrumentos fosse realizada. Os resultados demonstraram que não houve diferença estatisticamente significante entre os grupos, embora tenha sido observado um desgaste mais uniforme nas paredes dentinárias pela instrumentação com os sistemas Profile e Endo-Eze associados

Avaliação da citotoxicidade de materiais obturadores de canais radiculares: influência na liberação de fator de necrose tumoral-alfa e interferon-y e óxido nítrico em cultura de células murinas / Evaluation of the citotoxicity of endodontic sealers: influency on liberation of tumor necrotic factor-alpha, interferon gamma and nitric oxide in murine cells culture

Os macrófagos constituem uma população celular do sistema imune. Estas células podem ser ativadas por uma variedade de estímulos e suas principais funções incluem a fagocitose de partículas estranhas, apresentação de antígenos, produção de citocinas e compostos intermediários do nitrogênio (NO) e do oxigênio (H2O2). Os cimentos endodônticos são capazes de promover uma estimulação do sistema imune. Neste estudo, foram analisados os níveis de quantificação das citocinas, além do mediador óxido nítrico, como uma medida de estimulação de macrófagos peritoneais de camundongos. Através de análise estatística de dados, foram observados os níveis de citotoxidade dos macrófagos de camundongos estimulados pelos diferentes cimentos endodônticos, meio RPMI-1640 (grupo controle -) e LPS (grupo controle +). Os diferentes cimentos testados apresentaram concentrações com diferentes citotoxicidades: Sealapex 35 ug/ml, Polímero de Mamona 8,75 ug/ml, do Epiphany + Primer 17,5 ug/ml, do Primer 35 ug/ml, do EndoRez 17,5 ug/ml e do AH Plus 70 ug/ml. Após a adequação das concentrações viáveis dos cimentos testados conclui-se que o material que mais estimulou a liberação de NO foi Primer, seguido do Endorez, AH Plus, Epiphany, Sealapex, Epiphany + Primer. O Polímero de Mamona foi o que estimulou a uma menor produção de NO. Em relação à produção de TNF-alfa o material que estimulou maior produção foi o Primer, seguido de Epiphany, AH Plus, Epiphany + Primer, Sealapex e Polímero de Mamona. O EndoRez não foi capaz de estimular a produção de TNF-alfa. Nenhum dos cimentos testados induziu à liberação de IFN-y, sugerindo que outros mediadores tais como IL-1 e IL-12 possam estar envolvidos na liberação de NO observada no presente estudo

It was evaluated the citotoxicity of the sealers, Sealapex, Polímero de Mamona, Epiphany, EndoRez and AH Plus in relation to the release of Nitric Oxide, Tumor Necrotic Factor-Alpha and Interferon Gamma in murine cells culture. After the ideal concentration was found, according to MTT test, it was conduded that the sealers with higher release were Polímero de Mamona, EndoRez, Epiphany + Primer, Epiphany, Primer do Epiphany - Sealapex and AH Plus. All sealers reached lower levels of citotoxicity than control

Avaliação da citotoxicidade de materiais obturadores de canais radiculares: influência na liberação de fator de necrose tumoral-alfa e interferon-y e óxido nítrico em cultura de células murinas / Evaluation of the citotoxicity of endodontic sealers: influency on liberation of tumor necrotic factor-alpha, interferon gamma and nitric oxide in murine cells culture

Os macrófagos constituem uma população celular do sistema imune. Estas células podem ser ativadas por uma variedade de estímulos e suas principais funções incluem a fagocitose de partículas estranhas, apresentação de antígenos, produção de citocinas e compostos intermediários do nitrogênio (NO) e do oxigênio (H2O2). Os cimentos endodônticos são capazes de promover uma estimulação do sistema imune. Neste estudo, foram analisados os níveis de quantificação das citocinas, além do mediador óxido nítrico, como uma medida de estimulação de macrófagos peritoneais de camundongos. Através de análise estatística dos dados, foram observados os níveis de citotoxicidade dos macrófagos de camundongos estimulados pelos diferentes cimentos endodônticos, meio RPMI-1640 (grupo controle) e LPS (grupo controle +). Os diferentes cimentos testados apresentaram concentrações com diferentes citotoxicidades: Sealapex 35 ug/ml, Polímero de Mamona 8,75 ug/ml, do Epiphany 17,5 ug/mle do AH Plus 70 ug/ml. Após a adequação das concentrações viáveis dos cimentos testados conclui-se que o material que mais estimulou a liberação de NO foi Primer...

Myotonic dystrophy protein kinase phosphorylates phospholamban and regulates calcium uptake in cardiomyocyte sarcoplasmic reticulum.

Myotonic dystrophy (DM) is caused by a CTG expansion in the 3'-untranslated region of a protein kinase gene (DMPK). Cardiovascular disease is one of the most prevalent causes of death in DM patients. Electrophysiological studies in cardiac muscles from DM patients and from DMPK(-/-) mice suggested that DMPK is critical to the modulation of cardiac contractility and to the maintenance of proper cardiac conduction activity. However, there are no data regarding the molecular signaling pathways involved in DM heart failure. Here we show that DMPK expression in cardiac myocytes is highly enriched in the sarcoplasmic reticulum (SR) where it colocalizes with the ryanodine receptor and phospholamban (PLN), a muscle-specific SR Ca(2+)-ATPase (SERCA2a) inhibitor. Coimmunoprecipitation studies showed that DMPK and PLN can physically associate. Furthermore, purified wild-type DMPK, but not a kinase-deficient mutant (K110A DMPK), phosphorylates PLN in vitro. Subsequent studies using the DMPK(-/-) mice demonstrated that PLN is hypo-phosphorylated in SR vesicles from DMPK(-/-) mice compared with wild-type mice both in vitro and in vivo. Finally, we show that Ca(2+) uptake in SR is impaired in ventricular homogenates from DMPK(-/-) mice. Together, our data suggest the existence of a novel regulatory DMPK pathway for cardiac contractility and provide a molecular mechanism for DM heart pathology.