Prognostic utility of the assessment of diastolic function in patients undergoing cardiac resynchronization therapy.

Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function. Aims of the study are to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. METHODS AND RESULTS: One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III. CRT-response, defined as a reduction of left ventricular (LV) end-systolic volume > 15% at 6-month follow-up (FU), occurred in 132 (68%) patients. The primary endpoint was a composite of heart transplantation, LV assisted device implantation, or all-cause death during FU and occurred in 29 (15%) patients. CRT was associated with a degradation of DD in non-responders. At multivariable analysis corrected for clinical variables, QRS duration, mitral regurgitation, CRT-response and LV dyssynchrony, grade I DD was associated with a better outcome (HR 0.37, 95% CI: 0.14-0.96). Non-responders with grade II-III DD had the worse prognosis (HR 4.36, 95%CI: 2.10-9.06). CONCLUSIONS: The evaluation of DD in CRT candidates allows the prognostic stratification of patients, independently from CRT-response.

Na(+) dependence of K(+) -induced natriuresis, kaliuresis and Na(+) /Cl(-) cotransporter dephosphorylation.

AIM: High dietary K(+) intake is associated with protection against hypertension. In mammals, acute K(+) intake induces natriuresis and kaliuresis, associated with a marked dephosphorylation of the renal Na(+) /Cl(-) cotransporter (NCC). It has been suggested that reduced activity of NCC increases the driving force for more distal tubular epithelial Na(+) channel (ENaC)-dependent K(+) secretion. This study investigated the ENaC dependence of urinary K(+) and Na(+) excretion following acute K(+) loading. METHODS: Mice were fed low (0.03%), control (0.2%) or high (2%) Na(+) diets for 25 days to preserve or promote Na(+) loss and thus ENaC activity. Once a week, the mice received either K(+) -containing gavage or a control gavage. Following the gavage treatment, the mice were placed in metabolic cages and urine was collected in real time. ENaC dependence of kaliuresis was assessed by benzamil injections prior to gavage. RESULTS: We confirmed that dietary Na(+) content is inversely related to plasma aldosterone, NCC phosphorylation and ENaC cleavage products. The novel findings were as follows: (i) acute K(+) feeding caused NCC dephosphorylation in all dietary groups; (ii) under all dietary conditions, K(+) loading induced natriuresis; (iii) high Na(+) diet markedly reduced the K(+) excretion following K(+) gavage; (iv) benzamil injection prior to K(+) loading increased natriuresis, decreased kaliuresis and eliminated the differences between the dietary groups. CONCLUSION: These data indicate that acute K(+) -induced kaliuresis is ENaC dependent. Maximal K(+) excretion rates are attenuated when ENaC is physiologically down-regulated or pharmacologically blocked. NCC is dephosphorylated following acute K(+) loading under all dietary Na(+) regimens. This leads to natriuresis, even in severely Na(+) -restricted animals.