Adrenergic stimulation modulates excitation-contraction coupling (ECC) and cardiac function primarily through protein kinase A (PKA), which phosphorylates multiple ECC proteins. Key PKA targets include phospholamban (PLB), a critical regulator of SERCA2-mediated Ca2+ uptake. Previous studies using transgenic overexpression of non-phosphorylatable PLB reported that Ca2+ release and inotropy were partially preserved in response to adrenergic stimulation; however, this model may be confounded by transgene insertion and other compensatory mechanisms. To address these limitations, we used CRISPR/Cas9 to generate a mouse model with genomic mutations resulting in non-phosphorylatable substitutions at relevant residues in PLB (PLB-S16A/T17A, PLB-DM). Mass spectrometry confirmed the complete absence of PLB phosphorylation in PLB-DM hearts. PLB-DM mice displayed normal heart structure, mild bradycardia and reduced cardiac output. PLB-DM myocytes showed reduced Ca2+ transient amplitude and decay, and reduced SR Ca2+ load compared to WT controls under adrenergic stimulation. L-type Ca2+ current density and kinetics remained unaltered in PLB-DM myocytes, suggesting that previous reports of preserved inotropy likely reflected model-specific compensatory adaptations. These results suggest that PLB phosphorylation is required to achieve a complete cellular adrenergic response.

The haemodynamic mechanisms underlying vasovagal (reflex) syncope include hypotension and extrinsic asystole/bradycardia, corresponding to two distinct haemodynamic phenotypes of syncope, that is, the hypotensive and the bradycardic phenotypes. The hypotensive phenotype is the most prevalent, being observed in the 83% of patients. Twenty-four hours ambulatory blood pressure monitoring (ABPM) demonstrated high effectiveness in identifying the hypotensive phenotype in patients with suspected reflex syncope. The diagnosis of a hypotensive mechanism of syncope is supported by ABPM when one or more of the following criteria are present:. Constitutional hypotension: 24-h systolic blood pressure (SBP) < 105 mmHg in men and <98 in women. Drug-related hypotension: 24-h SBP <120 mmHg. Hypotensive episodes: ≥1 daytime SBP <90 mmHg or ≥2 daytime SBP <100 mmHg. Postprandial hypotension: symptomatic SBP fall >20 mmHg or absolute value <90 mmHg within 75 min of meals. ABPM also plays a key role in guiding therapy. In hypertensive patients with hypotensive syncope, deprescribing antihypertensive medications is indicated with the goal of increasing 24-h average SBP to ≥ 134 mmHg and/or by at least ≥12 mmHg, without exceeding 140 mmHg (or <160 mmHg in frail older patients). In patients with drug-unrelated hypotension, lower-body elastic garments, fludrocortisone, or midodrine-prescribed singularly or in combination-may be considered and targeted to achieve a 24-h average SBP ≥116 mmHg and/or an increase of at least ≥9 mmHg.

Severe hyperkalemia is a potentially fatal electrolyte disturbance that can produce a broad spectrum of cardiac conduction abnormalities. Although electrocardiographic changes classically follow a predictable progression, advanced atrioventricular block is an uncommon and often overlooked manifestation. We report the case of a 70-year-old woman with end-stage renal disease on maintenance hemodialysis who presented with altered mental status, profound bradycardia, and hypotension. Initial electrocardiography demonstrated complete atrioventricular block with a ventricular escape rhythm of 15-20 beats per minute. Laboratory evaluation confirmed severe hyperkalemia with a serum potassium level of 8.5 mmol/L. Despite prompt initiation of standard medical therapy, including intravenous calcium gluconate, insulin with glucose, and nebulized salbutamol, the patient remained hemodynamically unstable with no improvement in heart rate. Emergency temporary transvenous pacing was therefore performed, resulting in immediate hemodynamic stabilization. Definitive treatment with urgent hemodialysis led to normalization of serum potassium levels and complete recovery of normal sinus rhythm within 24 hours, allowing safe removal of the temporary pacemaker. This case highlights a rare and life-threatening presentation of hyperkalemia-induced complete atrioventricular block and underscores the limitations of medical therapy alone in advanced conduction disturbances. Early recognition and timely implementation of temporary transvenous pacing can be life-saving in hemodynamically unstable patients while definitive correction of hyperkalemia is achieved.

An 87-years-old woman with a history of right mastectomy for breast cancer, currently undergoing chemotherapy for multiple metastasis via a central venous catheter placed in the left subclavian vein, presented with bradycardia and dyspnea. Electrocardiogram revealed a 2:1 atrioventricular block. Implantation of a leadless pacemaker (LLPM) was planned for the patient. During implantation, right ventricular rupture occurred. Percutaneous cardiopulmonary support was initiated immediately. Subsequently, emergency surgery was performed. LLPM is considered a useful and safe device;however, serious complication, such as cardiac injury, have been reported in a small number of cases. Thorough risk assessment and preparation for complication, including cardiac surgery, may be life-saving.