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Background: The impact of the new heart allocation policy, which prioritizes acutely ill patients on temporary mechanical circulatory support and provides broader sharing of donor organs, on patient and graft survival in combined heart and kidney transplantation (HKT) is unknown. Methods: In the United Network for Organ Sharing data, patients were divided in groups before and after the policy change (OLD, January 1, 2015 to October 17, 2018, N=533; and NEW, October 18, 2018 to December 31, 2020, N=370). Propensity score matching was performed utilizing recipient characteristics (283 pairs). The median follow-up was 1099 days. Results: The annual volume of HKT increased approximately 2-fold during this period (N=117 in 2015 and N=237 in 2020), predominantly among patients not on hemodialysis at time of transplantation. Ischemic times for heart (OLD, 2.94 versus NEW, 3.37 hours; P P P P P =0.007), and graft failure among HKT recipients (heart, hazard ratio, 1.81; P =0.007; and kidney, hazard ratio, 1.83; P =0.002). Conclusions: The new heart allocation policy was associated with worse overall survival and decreased freedom from heart and kidney graft failure in HKT recipients.

Various pharmacotherapies exist for heart failure with preserved ejection fraction (HFpEF), but with unclear comparative efficacy. We searched EMBASE, Medline, and Cochrane Library from inception through August 2021 for all randomized clinical trials in HFpEF (EF40%) that evaluated beta-blockers, mineralocorticoid receptor antagonist (MRA), angiotensin-converting enzyme inhibitors (ACE), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Outcomes assessed were cardiovascular mortality, all-cause mortality, and HF hospitalization. A frequentist network meta-analysis was performed with a random-effects model. We included 22 randomized clinical trials (30,673 participants; mean age = 71.7 ± 4.2 years; females = 49.3 ± 7.7%; median follow-up = 24.4 ± 11.1 months). Compared with placebo, there was no statistically significant difference in cardiovascular mortality [beta-blockers; odds ratio (OR) 0.79 (0.46-1.34), MRA; OR 0.90 (0.70-1.14), ACE OR 0.95 (0.59-1.53), ARB; OR 1.02 (0.87-1.19), ARNI; OR 0.97 (0.74-1.26) and SGLT2i; OR 1.00 (0.84-1.18)] or all-cause mortality [beta blockers; OR 0.75 (0.54-1.04), MRA; OR 0.90 (0.75-1.08) ACE; OR 1.05 (0.71-1.54), ARB; OR 1.03 (0.91-1.15), ARNI; OR 0.99 (0.82-1.20) and SGLT2i; OR 1.00 (0.89-1.13)]. The certainty in these estimates was low or very low. There was a significantly reduction in HF hospitalization with the use of SGLT2i [OR 0.71 (0.62-0.82), moderate certainty], ARNI [OR 0.77 (0.63-0.94), low certainty], and MRA [OR 0.81 (0.66-0.98), moderate certainty]; with corresponding P scores of 0.84, 0.68, and 0.58, respectively. In HFpEF, the use of beta-blockers, MRA, ACE/ARB/ARNI, or SGLT2i was not associated with improved cardiovascular or all-cause mortality. SGLT2i, ARNI, and MRA reduced the risk of HF hospitalizations.

Sarcoidosis is a granulomatous disease with the potential of multiple organ system involvement and its etiology remains unknown. Cardiac involvement is associated with worse clinical outcome, and has been reported to be 20%-30% in Caucasian and as high as 58% in Japanese populations with sarcoidosis. Clinical manifestations of cardiac sarcoidosis highly depend on the extent and location of granulomatous inflammation. The most frequent presentations include heart block, tachyarrhythmia, or heart failure. Endomyocardial biopsy is the most specific diagnostic test, but has poor sensitivity due to often patchy involvement. The diagnosis of cardiac sarcoidosis remains challenging due to non-specific imaging findings. Both 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and cardiac magnetic resonance imaging can be used to evaluate cardiac sarcoidosis, but evaluate different stages of the disease process. FDG-PET detects metabolically-active inflammatory cells while cardiac magnetic resonance imaging with late gadolinium enhancement reveals areas of myocardial necrosis and fibrosis. Aggressive therapy of symptomatic cardiac sarcoidosis is often sought due to the high risk of sudden death and/or progression to heart failure. Prednisone 20-40 mg a day is the recommended initial treatment. In refractory or severe cases, higher doses of prednisone, 1 to 1.5 mg/kg/day (or its equivalent) and addition of a steroid sparing agent have been utilized. Methotrexate is added most commonly. Long-term improvement has been reported with the use of a combination of weekly methotrexate and prednisone versus prednisone alone. After initiation of treatment, a cardiac FDG-PET scan may be performed 2-3 months later to assess treatment response.

Background: Coronary angiography to identify coronary artery disease has been foundational to distinguish the cause of dilated cardiomyopathy (DCM), including the assignment of idiopathic or ischemic cardiomyopathy. Late gadolinium enhancement (LGE) with cardiovascular magnetic resonance (CMR) has emerged as an approach to identify myocardial scar and identify etiology. Methods: The DCM Precision Medicine Study included patients with left ventricular dilation and dysfunction attributed to idiopathic DCM, after expert clinical review excluded ischemic or other cardiomyopathies. Ischemic cardiomyopathy was defined as coronary artery disease with >50% narrowing at angiography of ≥1 epicardial coronary artery. CMR was not required for study inclusion, but in a post hoc analysis of available CMR reports, patterns of LGE were classified as (1) no LGE, (2) ischemic-pattern LGE: subendocardial/transmural, (3) nonischemic LGE: midmyocardial/epicardial. Results: Of 1204 idiopathic DCM patients evaluated, 396 (32.9%) had a prior CMR study; of these, 327 (82.6% of 396) had LGE imaging (mean age 46 years; 53.2% male; 55.4% White); 178 of the 327 (54.4%) exhibited LGE, and 156 of the 178 had LGE consistent with idiopathic DCM. The remaining 22 had transmural or subendocardial LGE. Of these 22, coronary angiography was normal (13), showed luminal irregularities (3), a distant thrombus (1), coronary artery disease with Conclusions: Of 327 probands enrolled in the DCM Precision Medicine Study cohort who had LGE-CMR data available, an ischemic-pattern of LGE was identified in 22 (6.7%), all of whom had idiopathic DCM as adjudicated by expert clinical review. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03037632.

Introduction: There is limited evidence demonstrating the benefit of hemodynamics in diagnosing the etiology of cardiomyopathy in patients referred for advanced therapies such as left ventricular assist device (LVAD) or orthotropic heart transplantation (OHT). Hypothesis: In patients with end stage heart failure, invasive hemodynamic measures differ between patients with different etiologies of cardiomyopathy. Methods: Hemodynamic and echocardiography data from 119 patients undergoing LVAD (n=85, Male 76%, Age 63 ± 12 years) or OHT (n=34, Male 70%, Age 60 ± 11 years) at a single center was reviewed. The follow invasive hemodynamic measurements were recorded and compared (central venous pressure (CVP), Pulmonary Artery Pulsatility Index (PAPI), peripheral vascular resistance (PVR), transpulmonary gradient, mean pulmonary artery pressure, cardiac index, and pulmonary diastolic pressure decoupling) were compared between groups. Results: Between patients with dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), and those with missed diagnosis, there were no significant differences between CVP, PAPI, PVR, transpulmonary gradient, mean PA pressure, cardiac index, or decoupling (Table 1). Left ventricular end diastolic diameter (LVEDD) on echocardiography was significantly larger in patients with DCM when compared to those with ischemic cardiomyopathy as well as infiltrative cardiomyopathies (6.65±1.04mm, 6.24±0.77mm, and 5.14±1.25mm, respectively p Conclusions: Hemodynamic measures in patients with stage D cardiomyopathy did not differ according to the etiology of the underlying cardiomyopathy. . The similarity in hemodynamic profiles amongst different cardiomyopathy subtypes likely reflects end stage disease. LVEDD performed better than hemodynamics to help differentiate cardiomyopathy etiologies, and in addition were helpful in identifying cases where the diagnosis was incorrect.

Background— The clinical significance of variants in genes associated with inherited cardiomyopathies can be difficult to determine because of uncertainty regarding population genetic variation and a surprising amount of tolerance of the genome even to loss-of-function variants. We hypothesized that genes associated with cardiomyopathy might be particularly resistant to the accumulation of genetic variation. Methods and Results— We analyzed the rates of single nucleotide genetic variation in all known genes from the exomes of >5000 individuals from the National Heart, Lung, and Blood Institute’s Exome Sequencing Project, as well as the rates of structural variation from the Database of Genomic Variants. Most variants were rare, with over half unique to 1 individual. Cardiomyopathy-associated genes exhibited a rate of nonsense variants, about 96.1% lower than other Mendelian disease genes. We tested the ability of in silico algorithms to distinguish between a set of variants in MYBPC3 , MYH7 , and TNNT2 with strong evidence for pathogenicity and variants from the Exome Sequencing Project data. Algorithms based on conservation at the nucleotide level (genomic evolutionary rate profiling, PhastCons) did not perform as well as amino acid-level prediction algorithms (Polyphen-2, SIFT). Variants with strong evidence for disease causality were found in the Exome Sequencing Project data at prevalence higher than expected. Conclusions— Genes associated with cardiomyopathy carry very low rates of population variation. The existence in population data of variants with strong evidence for pathogenicity suggests that even for Mendelian disease genetics, a probabilistic weighting of multiple variants may be preferred over the single gene causality model.