Reduction of left ventricular diastolic pressure as a key regulator of infarct coronary flow under mechanical left ventricular support.

Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Acute mechanical left ventricular (LV) support has been suggested to improve infarct tissue perfusion. However, its regulatory mechanism remains unclear. We investigated the physiological mechanisms in six Yorkshire pigs, which were subjected to 90-min balloon occlusion of the left anterior descending artery. During the acute reperfusion phase, LV support using an Impella heart pump was initiated. LV pressure, coronary flow and pressure of the infarct artery were simultaneously recorded to evaluate the impact of LV support on coronary physiology. Coronary wave intensity was calculated to understand the forces regulating coronary flow. Significant increases in coronary flow velocity and its area under the curve were found after mechanical LV support. Among the coronary flow-regulating factors, coronary pressure was increased mainly during the late diastolic phase with less pulsatility. Meanwhile, LV pressure was reduced throughout diastole resulting in significant and consistent elevation of coronary driving pressure. Interestingly, the duration of diastole was prolonged with LV support. In the wave intensity analysis, the duration between backward suction and pushing waves was extended, indicating that earlier myocardial relaxation and delayed contraction contributed to the extension of diastole. In conclusion, mechanical LV support increases infarct coronary flow by extending diastole and augmenting coronary driving pressure. These changes were mainly driven by reduced LV diastolic pressure, indicating that the key regulator of coronary flow under mechanical LV support is downstream of the coronary artery, rather than upstream. Our study highlights the importance of LV diastolic pressure in infarct coronary flow regulation. KEY POINTS: Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Although mechanical left ventricular (LV) support has been suggested to improve infarct coronary flow, its specific mechanism remains to be clarified. LV support reduced LV pressure, and elevated coronary pressure during the late diastolic phase, resulting in high coronary driving pressure. This study demonstrated for the first time that mechanical LV support extends diastolic phase, leading to increased infarct coronary flow. Future studies should evaluate the correlation between improved infarct coronary flow and resulting infarct size.

Risk stratification for isolated tricuspid valve surgery assisted using the Model for End-Stage Liver Disease score.

OBJECTIVE: Isolated tricuspid valve surgery is perceived as high-risk. This perception is nurtured by patients who often present with substantial liver dysfunction, which is inappropriately reflected in current surgical risk scores (eg, the Society of Thoracic Surgeons [STS] score has no specific tricuspid model). The Model for End-Stage Liver Disease (MELD) has was developed as a measure for the severity of liver dysfunction. We report scores and outcomes for our patient population. METHODS: We calculated STS, European System for Cardiac Operative Risk Evaluation (EuroSCORE) II (ESII), and MELD scores for all of our patients who received isolated tricuspid valve surgery between 2011 and 2020 (n = 157). We determined the MELD score, stratified patients into 3 groups (MELD <10: low, n = 53; 10 to <20: intermediate, n = 78; ≥20: high, n = 26) and describe associated outcomes. RESULTS: Patients were 72 ± 10 years old and 43% were male. Mean STS score was 4.9 ± 3.5% and ESII was 7.2 ± 6.6%. Mortality was 8.9% at 30 days and 65% at latest follow-up (95% CI, 51%-76%). Median follow-up was 4.4 years (range, 0-9.7 years). Although ESII and STS score accurately predicted 30-day mortality at low MELD scores (observed to expected [O/E] for ESII score = 0.8 and O/E for STS score = 1.0) and intermediate MELD (O/E for ESII score = 0.7, O/E for STS score = 1.0), mortality was underestimated at high MELD (O/E for ESII score = 3.0, O/E for STS score = 4.7). This subgroup also had higher incidence of new-onset hemodialysis. Besides MELD category, recent congestive heart failure, endocarditis, and hemodialysis were also associated with 30-day mortality. CONCLUSIONS: For isolated tricuspid valve regurgitation, classic surgical risk stratification with STS or ESII scores failed to predict perioperative mortality if there was evidence of severe liver dysfunction. Preoperative MELD assessment might be useful to assist in proper risk assessment for isolated tricuspid valve surgery.

Mitochondrial pyruvate carriers are required for myocardial stress adaptation.

In addition to fatty acids, glucose and lactate are important myocardial substrates under physiologic and stress conditions. They are metabolized to pyruvate, which enters mitochondria via the mitochondrial pyruvate carrier (MPC) for citric acid cycle metabolism. In the present study, we show that MPC-mediated mitochondrial pyruvate utilization is essential for the partitioning of glucose-derived cytosolic metabolic intermediates, which modulate myocardial stress adaptation. Mice with cardiomyocyte-restricted deletion of subunit 1 of MPC (cMPC1-/-) developed age-dependent pathologic cardiac hypertrophy, transitioning to a dilated cardiomyopathy and premature death. Hypertrophied hearts accumulated lactate, pyruvate and glycogen, and displayed increased protein O-linked N-acetylglucosamine, which was prevented by increasing availability of non-glucose substrates in vivo by a ketogenic diet (KD) or a high-fat diet, which reversed the structural, metabolic and functional remodelling of non-stressed cMPC1-/- hearts. Although concurrent short-term KDs did not rescue cMPC1-/- hearts from rapid decompensation and early mortality after pressure overload, 3 weeks of a KD before transverse aortic constriction was sufficient to rescue this phenotype. Together, our results highlight the centrality of pyruvate metabolism to myocardial metabolism and function.