Coronary artery disease (CAD) is the leading cause of mortality, with percutaneous coronary intervention (PCI) constituting the gold standard treatment. However, in an important proportion of the cases, lesion severity is debatable since conventional angiography provides only a two-dimensional representation of the vessel lumen and fails to quantify ischemic significance or plaque morphology. In these cases, several adjunctive tools considering physiology and imaging guidance may assist in quantifying the severity of the disease. Imaging modalities such as intravascular ultrasonography (IVUS) and optical coherence tomography (OCT), as well as physiology such as fractional flow reserve (FFR) and instantaneous wave-free (iFR), revolutionized revascularization strategy by linking anatomical stenosis to its functional consequence on myocardial perfusion. The present review summarizes and contrasts the available evidence for physiology and imaging guidance, considering the assessment of intermediate lesions during PCI and providing insights for their use in specific lesion subsets.

Background/Objectives: About one-third of patients who receive cardiac resynchronization therapy (CRT) do not show meaningful clinical improvement. One possible reason is that current criteria for diagnosing left bundle branch block (LBBB) do not clearly separate true conduction block from other conditions that can produce a similar QRS pattern, since they rely mainly on surface ECG features. The Strauss criteria have been proposed as a stricter alternative. They include sex-specific QRS duration thresholds and require a mid-QRS notch or slur, with the goal of better identifying patients whose conduction abnormality may be correctable. Selecting candidates on this basis reflects a personalized-medicine approach that matches resynchronization to the individual conduction substrate rather than applying a single wide-QRS threshold to all patients. In this review, we assess whether LBBB defined by the Strauss criteria is linked to better CRT outcomes, and we examine how these criteria have been used in the design of randomized clinical trials investigating conduction system pacing (CSP). Methods: A systematic search of PubMed, EMBASE, and the Cochrane Library was conducted (last updated April 2026) in accordance with PRISMA 2020 guidelines. Evidence was drawn from two groups of studies: (1) observational studies comparing CRT outcomes in Strauss-positive versus Strauss-negative patients, and (2) randomized CSP trials conducted in populations enriched using either Strauss-type or typical LBBB morphology. Results: A total of 17 comparative studies (n ≈ 4200) were included in Part 1; most (14 of 17) reported outcomes favouring Strauss-defined LBBB, with the greatest signal in non-ischemic cardiomyopathy, although these were mostly small retrospective studies with heterogeneous outcome definitions. However, two large registry analyses found no incremental benefit of strict over conventional criteria. In Part 2, six randomized controlled trials were analyzed. The HeartSync-LBBP trial (n = 200, 36-month follow-up) demonstrated significantly lower rates of mortality or heart failure hospitalization with LBBP compared to BiVP (8% vs. 28%; HR 0.26; 95% CI 0.12–0.57), with 98% technical success for LBBP. In contrast, the PhysioSync-HF trial (n = 173) showed superiority of BiVP, with CSP success of only 69% and 42.8% of procedures performed by less experienced operators. Similarly, the LEFT-BUNDLE-CRT trial (n = 176) found that LBBAP did not meet non-inferiority criteria compared to BiVP (RR 0.95; 95% CI 0.88–1.02). Conclusions: Strauss-defined LBBB is associated with improved CRT outcomes in observational studies, particularly in non-ischemic cardiomyopathy; this reflects an association rather than established superiority or causal benefit, and no randomized trial has yet compared Strauss-guided against guideline-based patient selection. In randomized CSP trials, both operator experience and patient selection appear to be critical determinants of success. BiVP remains effective even in patients meeting strict Strauss criteria. Further research is needed to determine whether the application of Strauss criteria improves outcomes beyond current guideline-based patient selection.