BACKGROUND: Alternative splicing plays crucial roles in normal heart development and cardiac disease by influencing protein-coding sequences, functional domains, and molecular networks. However, a detailed characterization of the human heart isoform landscape remains incomplete. METHODS: Leveraging long-read single-nucleus RNA sequencing and computational analysis, we dissected full-length isoform heterogeneities, expression patterns, and usage shifts across cell types, cell states, and cardiac conditions of the adult left ventricle. We applied in silico approaches to assess the functional relevance of identified isoforms; validated isoform compositions of representative cardiac genes using reverse transcription quantitative polymerase chain reaction and targeted amplicon sequencing; and developed a web server for interactive navigation of our results. RESULTS: The data revealed that isoform heterogeneity is widespread in the cardiac cellular system, serving as a posttranscriptional buffer mechanism that calibrates the molecule reservoirs in human hearts. In healthy left ventricles, ≈30% of cell type–specific genes were polyform, using multiple isoforms tailored to cell type–specific programs. Among ubiquitously expressed genes, >300 showed differential isoform usage with cell type specificity in normal hearts. Comparisons of cardiomyocytes across conditions uncovered 379 genes with marked isoform usage shifts, most of which are predicted to change protein coding outcomes through direct changes in protein coding sequences and switches between intron retention and non–protein-coding biotypes. In contrast, cell state–specific programs tend to operate on monoform genes associated with changes among cell states. In addition, our data revealed heart failure–associated differential isoform usage events in stromal and immune cell types in the cardiac microenvironment. CONCLUSIONS: We present a comprehensive atlas of splicing isoforms in the normal adult heart and heart failure through long-read single-nucleus RNA sequencing and computational analyses. The results suggest crucial roles of isoforms in buffering core cellular programs and contributing to disease-associated cell states. The full-length details of these cell-specific isoforms serve as an important reference for downstream translational and mechanistic studies and are available on our online data portal at https://github.com/gaolabtools/heart-isoform-atlas .

Bacillus Cereus endocarditis is a rare condition which has been implicated in intravenous drug users, and in patients with prosthetic heart valves. We report a rare case of Bacillus Cereus infecting a permanent pacing wire.

Heart transplant recipients (HTX) have several risk factors for heart failure which can trigger pro-inflammatory and fibrosis factors and set into motion pathophysiologic changes leading to diastolic dysfunction and HFpEF. The objective of the study was to determine if HTX recipients with dyspnea have diastolic dysfunction and HFpEF. Twenty-five HTX were included. LV systolic and diastolic functions were evaluated using conductance catheters to obtain pressure volume loops. LV function was assessed at rest and during moderate intensity exercise of the upper extremities. A significant increase occurred in LV minimal pressure (3.7 ± 3.3 to 6.5 ± 3.5 mmHg) and end diastolic pressure or EDP (11.5 ± 4 to 18 ± 3.8 mmHg, both P < 0.01) with exercise. With exercise, the time constant of LV relaxation shortened in 2, was unchanged in 3, and increased in the remaining patients (group results: rest 40 ± 11.6 vs 46 ± 9 ms, P < 0.01). LV chamber stiffness constant was abnormally increased in all but 2 patients. Indices of LV systolic properties were normal at rest but failed to augment with exercise. In 15 who agreed to blood draw, inflammation and fibrosis markers were obtained. A significant association was observed between LV EDP and Pro-Col III N-terminal (r = 0.58, P = 0.024) and IL-1-soluble receptor (r = 0.59, P = 0.02) levels. HTX have diastolic dysfunction and can develop HFpEF several years after cardiac transplantation. The abnormally increased LV chamber stiffness and the prolongation or lack of shortening of the time constant of LV relaxation with exercise are the underlying reasons behind the observed changes in LV diastolic pressures with exercise.