Outcome of clinical management in relatives of sudden cardiac death victims.

BACKGROUND: International guidelines recommend clinical assessment of the surviving first-degree relatives of sudden cardiac death (SCD) victims to identify a probable cause of death and protect surviving relatives. Only few studies have reported the outcome of clinical management and follow-up of relatives to SCD victims. METHODS: We performed a retrospective cohort study of the clinical and genetic assessment of surviving relatives of SCD victims referred to the Clinic of Inherited Cardiac Diseases at Aarhus University Hospital, Denmark, between 1995 and 2016. We studied clinical and autopsy findings on all cases of SCD among children and adults. Relatives were followed for adverse cardiovascular events including cardiac hospitalization, new-onset heart failure, coronary heart disease, malignant syncope or documented malignant ventricular arrhythmias, and death. RESULTS: We included 292 relatives of 56 SCD victims. During a median (interquartile range) follow-up of 3.3 (1.6-4.7) years twelve relatives experienced an adverse cardiovascular event of which only five were related to the inherited cardiac disease in the family. One developed dilated cardiomyopathy and one tachycardia induced heart failure, five suffered from ventricular tachycardia or a malignant syncope and received a secondary prophylactic Implantable Cardioverter Defibrillator, three had a coronary heart disease event and two died from old age. CONCLUSION: Relatives of SCD victims have a low rate of adverse cardiac events when guideline-based assessment and care is applied.

Congestive heart failure in rats is associated with increased collecting duct vasopressin sensitivity and vasopressin type 2 receptor reexternalization.

A number of studies have shown that rats with congestive heart failure (CHF) have increased protein levels of the vasopressin (AVP)-regulated water channel aquaporin-2 (AQP2) even during conditions with unchanged circulating levels of AVP, suggesting an increase in the sensitivity of the AVP type 2 (V2) receptor in experimental CHF. The present study was aimed at investigating AVP signaling in rats with moderate CHF (left ventricular end diastolic pressure >10 mmHg; normal plasma AVP levels) induced by ligation of the left anterior descending coronary artery. Sham-operated rats were used as controls. Western blotting analyses revealed an increased abundance of AQP2 in renal cortex (+33 ± 9% of sham; P < 0.05) and in inner medulla (IM) (+54 ± 15% of sham; P < 0.05) in CHF rats compared with sham-operated controls. Dose-response studies on isolated collecting ducts (CDs) showed an increased accumulation of cAMP in response to AVP in CHF rats compared with controls. V2 receptor surface-binding studies in isolated IMCDs showed a marked and comparable AVP-induced V2 receptor internalization in response to AVP in both CHF and control rats. As expected V2 receptor surface binding remained low after AVP challenge in control rats. In contrast to this, V2 receptor surface binding returned to pre-AVP levels within 30 min in the CHF rats, indicating an obtained recycling ability of the V2 receptor in CHF. Together the results indicate the presence of an increased AVP sensitivity in the CDs from CHF rats, associated with an acquired recycling ability of the V2 receptor.

[Myocardial infarction in 22 year-old male with essential thrombocythaemia]. / Myokardieinfarkt hos 22-årig mand med essentiel trombocytose.

Essential thrombocythaemia (ET) is an acquired myeloproliferative disorder that causes thrombosis and haemorrhage. The association of myocardial infarction with ET is rare. We here describe a 22 year-old male patient with ET who presented with acute myocardial infarction. Coronary angiography showed multi-vessel thrombosis. Percutaneous coronary angioplasty was successfully performed. The patient was treated with abciximab after percutaneous coronary intervention. Bone marrow biopsy confirmed ET; treatment was started with interferon-alpha along with aspirin and clopidogrel without haemorrhagic complications.

Downregulation of aquaporin-1 in alveolar microvessels in lungs adapted to chronic heart failure.

The threshold pressure for lung edema formation is increased in severe chronic heart failure (CHF) due to reduced microvascular permeability. The water channel aquaporin-1 (AQP1) is present in the pulmonary microvascular endothelium, and a number of studies suggest the importance of AQP1 as a molecular determinant of pulmonary microvascular water transport. The present study examined the abundance and localization of AQP1 in lungs from rats with CHF. We used two different models of CHF: ligation of the left anterior descending coronary artery (LAD ligation) and aorta-banding (AB). Sham-operated rats served as controls. Echocardiographic verification of left ventricular dysfunction, enhanced left ventricular end-diastolic pressure, and right ventricular hypertrophy confirmed the presence of CHF. Western blotting of whole-lung homogenates revealed significant downregulation of AQP1 in LAD-ligated rats (24 h: 58 ± 5% of sham; 3 weeks: 8 ± 3% of sham; 9 weeks: 16 ± 6% of sham) and after AB (30 weeks: 37 ± 5% of sham), whereas the protein levels of the specific endothelial cell marker PECAM-1 was increased 3 weeks after LAD ligation (229 ± 20% of sham), but unchanged after 9 weeks and in the AB rats compared to controls. Immunohistochemical examination 3 weeks after LAD ligation showed intact labeling of PECAM-1 but an almost complete absence of AQP1 in the pulmonary alveolar microvessels in the CHF rats. These results suggest that downregulation of AQP1 in the alveolar microvessels may act as a compensatory mechanism to protect against formation of excessive pulmonary edema in CHF.